The expression of NDP kinase was intense in KA and SCC compared with BCC .

The expression of <protein>NDP kinase</protein> was intense in KA and SCC compared with BCC .


However , the difference of NDP kinase expression between KA and SCC was not statistically significant .

However , the difference of <protein>NDP kinase</protein> expression between KA and SCC was not statistically significant .


And there was no statistically significant difference in NDP kinase expression between SCC with metastasis and SCC without metastasis .

And there was no statistically significant difference in <protein>NDP kinase</protein> expression between SCC with metastasis and SCC without metastasis .


Our results contradict the hypothesis concerning the possible role of nm23 gene as a metastatic suppressor gene in human skin cancer .

Our results contradict the hypothesis concerning the possible role of <dna>nm23 gene</dna> as a metastatic suppressor gene in human skin cancer .


The mechanism of overexpression in various tumor cell types and its biological significance in cutaneous carcinogenesis remain to be determined .

The mechanism of overexpression in various <cell_type>tumor cell types</cell_type> and its biological significance in cutaneous carcinogenesis remain to be determined .


RB and a novel E2F-1 binding protein in MHC class II deficient B-cell lines and normal IFN-gamma induction of the class IL transactivator CIITA in class II non-inducible RB-defective tumor lines .

<protein>RB</protein> and a novel <protein>E2F-1 binding protein</protein> in <cell_line>MHC class II deficient B-cell lines</cell_line> and normal <protein>IFN-gamma</protein> induction of the <dna>class IL transactivator</dna> <dna>CIITA</dna> in <cell_line>class II non-inducible RB-defective tumor lines</cell_line> .


The major histocompatibility ( MHC ) class II genes encode cell surface proteins that bind antigenic peptide for presentation to T-cells .

The <dna>major histocompatibility ( MHC ) class II genes</dna> encode <protein>cell surface proteins</protein> that bind antigenic peptide for presentation to <cell_type>T-cells</cell_type> .


The class II proteins are expressed constitutively on B-cells and EBV-transformed B-cells , and are inducible by IFN-gamma on a wide variety of cell types .

The <protein>class II proteins</protein> are expressed constitutively on <cell_type>B-cells</cell_type> and <cell_line>EBV-transformed B-cells ,</cell_line> and are inducible by <protein>IFN-gamma</protein> on a wide variety of <cell_type>cell types</cell_type> .


Retinoblastoma protein ( RB ) is a tumor suppressor and functions as a transcriptional repressor by binding and inactivating the transactivator E2F-I .

<protein>Retinoblastoma protein</protein> ( <protein>RB</protein> ) is a tumor suppressor and functions as a <protein>transcriptional repressor</protein> by binding and inactivating the <dna>transactivator E2F-I</dna> .


RB-defective tumor lines are non-inducible for MHC class II by IFN-gamma , or very weakly inducible , but transfection of 2 different lines with RB expression vectors re-establishes or substantially enhances class II inducibility .

<cell_line>RB-defective tumor lines</cell_line> are non-inducible for <protein>MHC class II</protein> by <protein>IFN-gamma</protein> , or very weakly inducible , but transfection of 2 different lines with <dna>RB expression vectors</dna> re-establishes or substantially enhances class II inducibility .


Therefore , we examined the RB status of a series of B-cell mutants that are defective in class II expression , generated either in vitro or derived from Bare Lymphocyte Syndrome ( BLS ) patients .

Therefore , we examined the <protein>RB</protein> status of a series of B-cell mutants that are defective in class II expression , generated either in vitro or derived from Bare Lymphocyte Syndrome ( BLS ) patients .


Nuclear matrix-bound RB was detectable in all cases , indicating that loss of RB is not responsible for decreased class II expression in these lines .

Nuclear matrix-bound <protein>RB</protein> was detectable in all cases , indicating that loss of <protein>RB</protein> is not responsible for decreased class II expression in these lines .


A second E2F-I binding protein , most likely DP-I , was also apparently normal in both class II-positive and -negative B-cell lines .


We also examined the IFN-gamma induction of CIITA in RB -defective lines .

We also examined the <protein>IFN-gamma</protein> induction of <dna>CIITA</dna> in <protein>RB</protein> -defective lines .


CIITA is a class II gene transactivator known to be defective in one form of BLS and to be required for the induction of MHC class II by IFN-gamma .

<dna>CIITA</dna> is a <dna>class II gene transactivator</dna> known to be defective in one form of BLS and to be required for the induction of <protein>MHC class II</protein> by <protein>IFN-gamma</protein> .


CIITA mRNA is normally inducible by IFN-gamma in class II non-inducible , RB-defective lines , and in one line , re-expression of RB has no effect on CIITA mRNA induction levels .

<rna>CIITA mRNA</rna> is normally inducible by <protein>IFN-gamma</protein> in <cell_line>class II non-inducible , RB-defective lines</cell_line> , and in one line , re-expression of <protein>RB</protein> has no effect on <rna>CIITA mRNA</rna> induction levels .


Thus , the block in MHC class II inducibility in RB-defective cells is not due to a block in CIITA inducibility .

Thus , the block in MHC class II inducibility in <cell_line>RB-defective cells</cell_line> is not due to a block in <dna>CIITA</dna> inducibility .


Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes .

<protein>Interleukin 12</protein> induces tyrosine phosphorylation and activation of <protein>STAT4</protein> in <cell_type>human lymphocytes</cell_type> .


Interleukin 12 ( IL-12 ) is an important immunoregulatory cytokine whose receptor is a member of the hematopoietin receptor superfamily .

<protein>Interleukin 12</protein> ( <protein>IL-12</protein> ) is an important <protein>immunoregulatory cytokine</protein> whose receptor is a member of the <protein>hematopoietin receptor superfamily</protein> .


We have recently demonstrated that stimulation of human T and natural killer cells with IL-12 induces tyrosine phosphorylation of the Janus family tyrosine kinase JAK2 and Tyk2 , implicating these kinases in the immediate biochemical response to IL-12 .

We have recently demonstrated that stimulation of <cell_type>human T and natural killer cells</cell_type> with <protein>IL-12</protein> induces tyrosine phosphorylation of the <protein>Janus family tyrosine kinase</protein> <protein>JAK2</protein> and <protein>Tyk2</protein> , implicating these <protein>kinases</protein> in the immediate biochemical response to <protein>IL-12</protein> .


Recently , transcription factors known as STATs ( signal transducers and activators of transcription ) have been shown to be tyrosine phosphorylated and activated in response to a number of cytokines that bind hematopoietin receptors and activate JAK kinases .

Recently , <protein>transcription factors</protein> known as <protein>STATs</protein> ( <protein>signal transducers and activators of transcription</protein> ) have been shown to be tyrosine phosphorylated and activated in response to a number of <protein>cytokines</protein> that bind <protein>hematopoietin receptors</protein> and activate <protein>JAK kinases</protein> .


In this report we demonstrate that IL-12 induces tyrosine phosphorylation of a recently identified STAT family member , STAT4 , and show that STAT4 expression is regulated by T-cell activation .

In this report we demonstrate that <protein>IL-12</protein> induces tyrosine phosphorylation of a recently identified <protein>STAT family member</protein> , <protein>STAT4</protein> , and show that <protein>STAT4</protein> expression is regulated by T-cell activation .


Furthermore , we show that IL-12 stimulates formation of a DNA-binding complex that recognizes a DNA sequence previously shown to bind STAT proteins and that this complex contains STAT4 .

Furthermore , we show that <protein>IL-12</protein> stimulates formation of a <protein>DNA-binding complex</protein> that recognizes a DNA sequence previously shown to bind <protein>STAT proteins</protein> and that this complex contains <protein>STAT4</protein> .


These data , and the recent demonstration of JAK phosphorylation by IL-12 , identify a rapid signal-transduction pathway likely to mediate IL-12 -induced gene expression .

These data , and the recent demonstration of <protein>JAK</protein> phosphorylation by <protein>IL-12</protein> , identify a rapid signal-transduction pathway likely to mediate <protein>IL-12</protein> -induced gene expression .


Temperature-induced down-regulation of the glucocorticoid receptor in peripheral blood mononuclear leucocyte in patients with sepsis or septic shock .

Temperature-induced down-regulation of the <protein>glucocorticoid receptor</protein> in <cell_type>peripheral blood mononuclear leucocyte</cell_type> in patients with sepsis or septic shock .


OBJECTIVE : Activation of the hypothalamic-pituitary-adrenal axis is of vital importance during critical illness .


We have studied the adaptive mechanisms which occur at the level of the glucocorticoid receptor in glucocorticoid target tissues in patients with sepsis or septic shock .

We have studied the adaptive mechanisms which occur at the level of the <protein>glucocorticoid receptor</protein> in glucocorticoid target tissues in patients with sepsis or septic shock .


DESIGN : The effects of hypercortisolaemia , hyperthermia and cellular composition on number of glucocorticoid receptors per cell and their affinity were evaluated , both in vitro and in vivo , in peripheral blood mononuclear leucocytes of control subjects and in patients with sepsis or septic shock .

DESIGN : The effects of hypercortisolaemia , hyperthermia and cellular composition on number of <protein>glucocorticoid receptors</protein> per cell and their affinity were evaluated , both in vitro and in vivo , in <cell_type>peripheral blood mononuclear leucocytes</cell_type> of control subjects and in patients with sepsis or septic shock .


SUBJECTS : Fifteen patients ( age 25-79 ) with sepsis or septic shock who were admitted to an intensive care unit were studied .


The control group consisted of 24 healthy laboratory employees .


MEASUREMENTS : The binding capacity and affinity of the glucocorticoid receptors were measured and compared to clinical data and the plasma cortisol concentrations .

MEASUREMENTS : The binding capacity and affinity of the <protein>glucocorticoid receptors</protein> were measured and compared to clinical data and the plasma cortisol concentrations .


RESULTS : Hypercortisolaemia , in vitro , resulted in a decreased affinity and a decreased binding capacity of the glucocorticoid receptor .

RESULTS : Hypercortisolaemia , in vitro , resulted in a decreased affinity and a decreased binding capacity of the <protein>glucocorticoid receptor</protein> .


In vitro , hyperthermia as well as variations in the cellular composition did not influence the glucocorticoid receptor .


In vivo , there was no change in the number of receptors per cell in patients with sepsis or septic shock as compared to healthy controls .


However , a decreased affinity of the glucocorticoid receptor was observed .

However , a decreased affinity of the <protein>glucocorticoid receptor</protein> was observed .


There was a weak but significant negative correlation between body temperature and the number of glucocorticoid receptors in the patient group .

There was a weak but significant negative correlation between body temperature and the number of <protein>glucocorticoid receptors</protein> in the patient group .


There was no relation between circulating cortisol concentrations and glucocorticoid receptor affinity and number .

There was no relation between circulating cortisol concentrations and <protein>glucocorticoid receptor</protein> affinity and number .


CONCLUSIONS : There is no obvious regulation of the number of glucocorticoid receptors by plasma cortisol concentrations in vivo .

CONCLUSIONS : There is no obvious regulation of the number of <protein>glucocorticoid receptors</protein> by plasma cortisol concentrations in vivo .


The decreased affinity of the glucocorticoid receptor together with the negative correlation between hyperthermia and the number of glucocorticoid receptors in patients with sepsis or septic shock suggest that hypothalamic-pituitary-adrenal axis activation during critical illness is accompanied by peripheral adaptation in glucocorticoid receptor number and affinity .

The decreased affinity of the <protein>glucocorticoid receptor</protein> together with the negative correlation between hyperthermia and the number of <protein>glucocorticoid receptors</protein> in patients with sepsis or septic shock suggest that hypothalamic-pituitary-adrenal axis activation during critical illness is accompanied by peripheral adaptation in <protein>glucocorticoid receptor</protein> number and affinity .


Integrin-mediated tyrosine phosphorylation and cytokine message induction in monocytic cells .

Integrin-mediated tyrosine phosphorylation and <protein>cytokine</protein> message induction in <cell_type>monocytic cells</cell_type> .


A possible signaling role for the Syk tyrosine kinase .

A possible signaling role for the <protein>Syk tyrosine kinase</protein> .


Activation of cytoplasmic tyrosine kinases is an important aspect of signal transduction mediated by integrins .

Activation of <protein>cytoplasmic tyrosine kinases</protein> is an important aspect of signal transduction mediated by <protein>integrins</protein> .


In the human monocytic cell line THP-1 , either integrin -dependent cell adhesion to fibronectin or ligation of beta 1 integrins with antibodies causes a rapid and intense tyrosine phosphorylation of two sets of proteins of about 65-75 and 120-125 kDa .

In the <cell_line>human monocytic cell line THP-1</cell_line> , either <protein>integrin</protein> -dependent cell adhesion to <protein>fibronectin</protein> or ligation of beta 1 integrins with <protein>antibodies</protein> causes a rapid and intense tyrosine phosphorylation of two sets of proteins of about <protein>65-75 and 120-125 kDa</protein> .


In addition , integrin ligation leads to nuclear translocation of the p50 and p65 subunits of the NF-kappa B transcription factor , to activation of a reporter gene driven by a promoter containing NF-kappa B sites , and to increased levels of mRNAs for immediate-early genes , including the cytokine interleukin ( IL ) -1 beta .

In addition , <protein>integrin</protein> ligation leads to nuclear translocation of the <protein>p50</protein> and <protein>p65 subunits</protein> of the <protein>NF-kappa B transcription factor</protein> , to activation of a <dna>reporter gene</dna> driven by a <dna>promoter</dna> containing <dna>NF-kappa B sites</dna> , and to increased levels of <rna>mRNAs</rna> for <dna>immediate-early genes</dna> , including the <protein>cytokine interleukin ( IL ) -1 beta</protein> .


The tyrosine kinase inhibitors genistein and herbimycin A block both integrin -mediated tyrosine phosphorylation and increases in IL-1 beta message levels , indicating a causal relationship between the two events .

The tyrosine kinase inhibitors genistein and herbimycin A block both <protein>integrin</protein> -mediated tyrosine phosphorylation and increases in <protein>IL-1 beta</protein> message levels , indicating a causal relationship between the two events .


The components tyrosine phosphorylated subsequent to cell adhesion include paxillin , pp125FAK , and the SH2 domain containing tyrosine kinase Syk .

The components tyrosine phosphorylated subsequent to cell adhesion include <protein>paxillin</protein> , <protein>pp125FAK</protein> , and the <protein>SH2 domain containing tyrosine kinase Syk</protein> .


In contrast , integrin ligation with antibodies induces tyrosine phosphorylation of Syk but not of FAK or paxillin .

In contrast , <protein>integrin</protein> ligation with <protein>antibodies</protein> induces tyrosine phosphorylation of <protein>Syk</protein> but not of <protein>FAK</protein> or <protein>paxillin</protein> .


In adhering cells , pre-treatment with cytochalasin D suppresses tyrosine phosphorylation of FAK and paxillin but not of Syk , while IL-1 beta message induction is unaffected .

In <cell_type>adhering cells</cell_type> , pre-treatment with cytochalasin D suppresses tyrosine phosphorylation of <protein>FAK</protein> and <protein>paxillin</protein> but not of <protein>Syk</protein> , while <protein>IL-1 beta</protein> message induction is unaffected .


These observations indicate that the Syk tyrosine kinase may be an important component of an integrin signaling pathway in monocytic cells , leading to activation of NF-kappa B and to increased levels of cytokine messages .

These observations indicate that the <protein>Syk</protein> tyrosine kinase may be an important component of an <protein>integrin</protein> signaling pathway in <cell_type>monocytic cells</cell_type> , leading to activation of <protein>NF-kappa B</protein> and to increased levels of <protein>cytokine</protein> messages .


Inhibition of dexamethasone binding to human glucocorticoid receptor by New World primate cell extracts .

Inhibition of dexamethasone binding to <protein>human glucocorticoid receptor</protein> by New World primate cell extracts .


To determine if New World primates express an inhibitor that influences glucocorticoid receptor ( GR ) binding characteristics , we examined [ 3H ] dexamethasone binding in cytosol prepared from B95-8 lymphoid cells , derived from the cotton top tamarin ( Saguinus oedipus ) , in combination with cytosol prepared from human or rat tissues .

To determine if New World primates express an inhibitor that influences <protein>glucocorticoid receptor</protein> ( <protein>GR</protein> ) binding characteristics , we examined [ 3H ] dexamethasone binding in cytosol prepared from <cell_line>B95-8 lymphoid cells</cell_line> , derived from the cotton top tamarin ( Saguinus oedipus ) , in combination with cytosol prepared from human or rat tissues .


B95-8 cytosol inhibited specific binding of [ 3H ] dexamethasone ( P < 0.01 ) when mixed with cytosol prepared from either a human lymphoid cell line ( HL ) or rat thymus .

B95-8 cytosol inhibited specific binding of [ 3H ] dexamethasone ( P < 0.01 ) when mixed with cytosol prepared from either a <cell_line>human lymphoid cell line</cell_line> ( <cell_line>HL</cell_line> ) or rat thymus .


The inhibitory activity was heat labile and trypsin sensitive .

The inhibitory activity was heat labile and <protein>trypsin</protein> sensitive .


Peak inhibitory activity was found in the 150-200 kd fractions after Sephacryl G-200 ultrafiltration .


Scatchard analysis of [ 3H ] dexamethasone binding using mixed cytosol showed a diminished GR apparent binding affinity when compared to HL cytosol .

Scatchard analysis of [ 3H ] dexamethasone binding using mixed cytosol showed a diminished <protein>GR</protein> apparent binding affinity when compared to HL cytosol .


Kinetic studies using mixed cytosol indicated that B95-8 cytosol did not affect the apparent dissociation rate of [ 3H ] dexamethasone .


These data demonstrate that B95-8 cells contain a competitive inhibitor that prevents binding of dexamethasone to its cognate receptor .

These data demonstrate that <cell_type>B95-8 cells</cell_type> contain a competitive inhibitor that prevents binding of dexamethasone to its <protein>cognate receptor</protein> .


Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals .

Disruption of a <dna>GATA motif</dna> in the <dna>Duffy gene promoter</dna> abolishes <dna>erythroid gene</dna> expression in Duffy-negative individuals .


The mRNA for the Duffy blood group antigen , the erythrocyte receptor for the Plasmodium vivax malaria parasite , has recently been cloned and shown to encode a widely expressed chemokine receptor .

The <rna>mRNA</rna> for the <protein>Duffy blood group antigen</protein> , the <protein>erythrocyte receptor</protein> for the Plasmodium vivax malaria parasite , has recently been cloned and shown to encode a widely expressed <protein>chemokine receptor</protein> .


Here , we show that the Duffy antigen/chemokine receptor gene ( DARC ) is composed of a single exon and that most Duffy-negative blacks carry a silent FY*B allele with a single T to C substitution at nucleotide -46 .

Here , we show that the <dna>Duffy antigen/chemokine receptor gene</dna> ( <dna>DARC</dna> ) is composed of a single <dna>exon</dna> and that most Duffy-negative blacks carry a <dna>silent FY*B allele</dna> with a single T to C substitution at nucleotide -46 .


This mutation impairs the promoter activity in erythroid cells by disrupting a binding site for the GATA1 erythroid transcription factor .

This mutation impairs the promoter activity in <cell_type>erythroid cells</cell_type> by disrupting a <dna>binding site</dna> for the <protein>GATA1 erythroid transcription factor</protein> .


With the recent characterization of the FY*A and FY*B alleles , these findings provide the molecular basis of the Duffy blood group system and an explanation for the erythroid-specific repression of the DARC gene in Duffy-negative individuals .

With the recent characterization of the <dna>FY*A and FY*B alleles</dna> , these findings provide the molecular basis of the Duffy blood group system and an explanation for the erythroid-specific repression of the <dna>DARC gene</dna> in Duffy-negative individuals .


Activation of pp90rsk and early growth response-1 gene expression by pokeweed mitogen in human B cells .

Activation of <protein>pp90rsk</protein> and <dna>early growth response-1 gene</dna> expression by <protein>pokeweed mitogen</protein> in <cell_type>human B cells</cell_type> .


The present studies have examined the effects of pokeweed mitogen ( PWM ) on the induction of early growth response-1 gene ( EGR-1 ) in normal human B cells .

The present studies have examined the effects of <protein>pokeweed mitogen</protein> ( <protein>PWM</protein> ) on the induction of <dna>early growth response-1 gene</dna> ( <dna>EGR-1</dna> ) in <cell_type>normal human B cells</cell_type> .


PWM regulates EGR-1 gene expression by both transcriptional and post-transcriptional mechanisms .

<protein>PWM</protein> regulates <dna>EGR-1</dna> gene expression by both transcriptional and post-transcriptional mechanisms .


Transient transfection assays with EGR-1 promoter fragments linked to the chloramphenicol acetyltransferase ( CAT ) gene demonstrated that PWM induced EGR-1 transcription is conferred by the CArG motif ( C C [ AT ] 6GG ) in the EGR-1 promoter .

Transient transfection assays with <dna>EGR-1 promoter fragments</dna> linked to the <dna>chloramphenicol acetyltransferase ( CAT ) gene</dna> demonstrated that <protein>PWM</protein> induced <dna>EGR-1</dna> transcription is conferred by the <dna>CArG motif</dna> ( <dna>C C [ AT ] 6GG</dna> ) in the <dna>EGR-1 promoter</dna> .


The results further demonstrated the activation of S6 kinase ( pp90rsk ) , evidenced by phosphorylation of S6 and serum response factor ( SRF ) peptides , in PWM treated B cells .

The results further demonstrated the activation of <protein>S6 kinase</protein> ( <protein>pp90rsk</protein> ) , evidenced by phosphorylation of <protein>S6</protein> and serum response factor ( SRF ) peptides , in <cell_line>PWM treated B cells</cell_line> .


Taken together , these findings suggest that PWM is able to initiate an intracytoplasmic signalling cascade and EGR-1 induction in normal human B cells .

Taken together , these findings suggest that <protein>PWM</protein> is able to initiate an intracytoplasmic signalling cascade and <dna>EGR-1</dna> induction in <cell_type>normal human B cells</cell_type> .


A conserved motif in the promoters of several cytokines expressed by human Th2-type lymphocytes .

A <dna>conserved motif</dna> in the <dna>promoters</dna> of several <protein>cytokines</protein> expressed by <cell_line>human Th2-type lymphocytes</cell_line> .


We have recently found a novel conserved motif in the promoters of several T-cell-expressed cytokines [ human interleukin-2 , -4 , -5 and -13 and human and mouse granulocyte/macrophage-colony stimulating factor ( GM-CSF ) ] .

We have recently found a novel <dna>conserved motif</dna> in the <dna>promoters</dna> of several <protein>T-cell-expressed cytokines</protein> [ <protein>human interleukin-2 , -4 , -5 and -13</protein> and <protein>human and mouse granulocyte/macrophage-colony stimulating factor</protein> ( <protein>GM-CSF</protein> ) ] .


It contains a core sequence CTTGG ... CCAAG which is present as part of larger palindromic sequences in each gene .

It contains a <dna>core sequence</dna> CTTGG ... CCAAG which is present as part of larger <dna>palindromic sequences</dna> in each gene .


This suggest that they may interact with a new family of trans-acting factors .

This suggest that they may interact with a new family of <protein>trans-acting factors</protein> .


In transfection assays , the human GM-CSF element has a strong positive effect on the expression of a reporter gene by the human T cell line Jurkat J6 upon stimulation .

In transfection assays , the <dna>human GM-CSF element</dna> has a strong positive effect on the expression of a <dna>reporter gene</dna> by the <cell_line>human T cell line</cell_line> <cell_line>Jurkat J6</cell_line> upon stimulation .


In DNA mobility shift assays , this sequence can give either six different specific bands which are competed out by different parts of the sequence or one specific band which is competed out by each of the inverted repeats , depending on the reconstitution conditions .


In different genes , the core sequences are separated by integer numbers of helical turns .

In different <dna>genes</dna> , the <dna>core sequences</dna> are separated by integer numbers of helical turns .


Considering the strong positive regulatory effect of this element and its presence in several T-cell-expressed cytokine genes , it may be crucial to the coordinated expression of these cytokines in T helper cells .

Considering the strong positive regulatory effect of this <dna>element</dna> and its presence in several <dna>T-cell-expressed cytokine genes</dna> , it may be crucial to the coordinated expression of these <protein>cytokines</protein> in <cell_type>T helper cells</cell_type> .


cDNA cloning of a NGFI-B/nur77-related transcription factor from an apoptotic human T cell line .

<dna>cDNA</dna> cloning of a <protein>NGFI-B/nur77-related transcription factor</protein> from an <cell_line>apoptotic human T cell line</cell_line> .


A human T lymphoid cell line , PEER , dies by apoptosis in the presence of PMA and calcium ionophore .

A <cell_line>human T lymphoid cell line</cell_line> , <cell_line>PEER</cell_line> , dies by apoptosis in the presence of PMA and calcium ionophore .


A new gene , TINUR , was cloned from apoptotic PEER cells .

A new <dna>gene</dna> , <dna>TINUR</dna> , was cloned from <cell_line>apoptotic PEER cells</cell_line> .


The expression of the TINUR gene is induced within 1 h after the cross-linking of the T cell Ag receptor complex .

The expression of the <dna>TINUR gene</dna> is induced within 1 h after the cross-linking of the <protein>T cell Ag receptor complex</protein> .


TINUR belongs to the NGFI-B/nur77 family of the steroid receptor superfamily and is an orphan receptor .

<dna>TINUR</dna> belongs to the <protein>NGFI-B/nur77 family</protein> of the <protein>steroid receptor superfamily</protein> and is an <protein>orphan receptor</protein> .


TINUR binds to the same DNA sequence as NGFI-B/nur77 .

<dna>TINUR</dna> binds to the same <dna>DNA sequence</dna> as <protein>NGFI-B/nur77</protein> .


We also propose that the NGFI-B/nur77 family can be classified into two subtypes .

We also propose that the <protein>NGFI-B/nur77 family</protein> can be classified into two subtypes .


Aspirin inhibits nuclear factor-kappa B mobilization and monocyte adhesion in stimulated human endothelial cells .

Aspirin inhibits <protein>nuclear factor-kappa B</protein> mobilization and monocyte adhesion in <cell_line>stimulated human endothelial cells</cell_line> .


BACKGROUND : The induction of vascular cell adhesion molecule-1 ( VCAM-1 ) and E-selectin by tumor necrosis factor-alpha ( TNF ) is mediated by mobilization of the transcription factor nuclear factor-kappa B ( NF-kappa B ) .

BACKGROUND : The induction of <protein>vascular cell adhesion molecule-1</protein> ( <protein>VCAM-1</protein> ) and <protein>E-selectin</protein> by <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF</protein> ) is mediated by mobilization of the <protein>transcription factor</protein> <protein>nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) .


Since salicylates have been reported to inhibit NF-kappa B activation by preventing the degradation of its inhibitor I kappa B , we studied a potential inhibition of this pathway by acetylsalicylate ( aspirin ) in human umbilical vein endothelial cells ( HUVECs ) .

Since salicylates have been reported to inhibit <protein>NF-kappa B</protein> activation by preventing the degradation of its inhibitor <protein>I kappa B</protein> , we studied a potential inhibition of this pathway by acetylsalicylate ( aspirin ) in <cell_line>human umbilical vein endothelial cells</cell_line> ( <cell_line>HUVECs</cell_line> ) .


METHODS AND RESULTS : Gel-shift analyses demonstrated dose-dependent inhibition of TNF -induced NF-kappa B mobilization by aspirin at concentrations ranging from 1 to 10 mmol/L .

METHODS AND RESULTS : Gel-shift analyses demonstrated dose-dependent inhibition of <protein>TNF</protein> -induced <protein>NF-kappa B</protein> mobilization by aspirin at concentrations ranging from 1 to 10 mmol/L .


Induction of VCAM-1 and E-selectin surface expression by TNF was dose-dependently reduced by aspirin over the same range , while induction of intercellular adhesion molecule-1 ( ICAM-1 ) was hardly affected .

Induction of <protein>VCAM-1</protein> and <protein>E-selectin</protein> surface expression by <protein>TNF</protein> was dose-dependently reduced by aspirin over the same range , while induction of <protein>intercellular adhesion molecule-1</protein> ( <protein>ICAM-1</protein> ) was hardly affected .


Aspirin appeared to prevent VCAM-1 transcription , since it dose-dependently inhibited induction of VCAM-1 mRNA by TNF .

Aspirin appeared to prevent <protein>VCAM-1</protein> transcription , since it dose-dependently inhibited induction of <rna>VCAM-1 mRNA</rna> by <protein>TNF</protein> .


As a functional consequence , adhesion of U937 monocytes to TNF-stimulated HUVECs was markedly reduced by aspirin due to suppression of VCAM-1 and E-selectin upregulation .

As a functional consequence , adhesion of <cell_line>U937 monocytes</cell_line> to <cell_line>TNF-stimulated HUVECs</cell_line> was markedly reduced by aspirin due to suppression of <protein>VCAM-1</protein> and <protein>E-selectin</protein> upregulation .


These effects of aspirin were not related to the inhibition of cyclooxygenase activity , since indomethacin was ineffective .

These effects of aspirin were not related to the inhibition of <protein>cyclooxygenase</protein> activity , since indomethacin was ineffective .


CONCLUSIONS : Our data suggest that aspirin inhibits NF-kappa B mobilization , induction of VCAM-1 and E-selectin , and subsequent monocyte adhesion in endothelial cells stimulated by TNF , thereby providing an additional mechanism for therapeutic effects of aspirin .

CONCLUSIONS : Our data suggest that aspirin inhibits <protein>NF-kappa B</protein> mobilization , induction of <protein>VCAM-1</protein> and <protein>E-selectin</protein> , and subsequent monocyte adhesion in <cell_type>endothelial cells</cell_type> stimulated by <protein>TNF</protein> , thereby providing an additional mechanism for therapeutic effects of aspirin .


Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites .

Activation of <protein>NF-kappa B</protein> by <protein>phosphatase</protein> inhibitors involves the phosphorylation of <protein>I kappa B alpha</protein> at <protein>phosphatase 2A-sensitive sites</protein> .


Activation of NF-kappa B by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor , I kappa B alpha , although the underlying mechanism remains unclear .

Activation of <protein>NF-kappa B</protein> by various cellular stimuli involves the phosphorylation and subsequent degradation of its inhibitor , <protein>I kappa B alpha</protein> , although the underlying mechanism remains unclear .


In the present study , the role of serine/threonine phosphatases in the regulation of I kappa B alpha phosphorylation was investigated .

In the present study , the role of <protein>serine/threonine phosphatases</protein> in the regulation of <protein>I kappa B alpha</protein> phosphorylation was investigated .


Our studies demonstrate that incubation of human T cells with low concentrations ( approximately 1-5 nM ) of calyculin A or okadaic acid , potent inhibitors of protein phosphatase type 1 ( PP-1 ) and type 2A ( PP-2A ) , induces the phosphorylation of I kappa B alpha even in the absence of any cellular stimulus .

Our studies demonstrate that incubation of <cell_type>human T cells</cell_type> with low concentrations ( approximately 1-5 nM ) of calyculin A or okadaic acid , potent inhibitors of <protein>protein phosphatase type 1 ( PP-1 ) and type 2A</protein> ( <protein>PP-2A</protein> ) , induces the phosphorylation of <protein>I kappa B alpha</protein> even in the absence of any cellular stimulus .


This action of the phosphatase inhibitors , which is associated with the activation of the RelA.p50 NF-kappa B heterodimer , is not affected by agents that block the induction of I kappa B alpha phosphorylation by tumor necrosis factor alpha ( TNF-alpha ) .

This action of the phosphatase inhibitors , which is associated with the activation of the <protein>RelA.p50 NF-kappa B heterodimer</protein> , is not affected by agents that block the induction of <protein>I kappa B alpha</protein> phosphorylation by <protein>tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) .


Furthermore , the phosphorylated I kappa B alpha from calyculin A-treated cells , but not that from TNF-alpha-stimulated cells , is sensitive to PP-2A in vitro , suggesting the existence of fundamental differences in the phosphorylation of I kappa B alpha induced by the two different NF-kappa B inducers .

Furthermore , the <protein>phosphorylated I kappa B alpha</protein> from <cell_line>calyculin A-treated cells</cell_line> , but not that from <cell_line>TNF-alpha-stimulated cells</cell_line> , is sensitive to <protein>PP-2A</protein> in vitro , suggesting the existence of fundamental differences in the phosphorylation of <protein>I kappa B alpha</protein> induced by the two different <protein>NF-kappa B</protein> inducers .


However , induction of I kappa B alpha phosphorylation by both TNF-alpha and the phosphatase inhibitors is associated with the subsequent degradation of I kappa B alpha .

However , induction of <protein>I kappa B alpha</protein> phosphorylation by both <protein>TNF-alpha</protein> and the phosphatase inhibitors is associated with the subsequent degradation of <protein>I kappa B alpha</protein> .


We further demonstrate that TNF-alpha- and calyculin A-induced I kappa B alpha degradation exhibits similar but not identical sensitivities to a proteasome inhibitor .


Together , these results suggest that phosphorylation of I kappa B alpha , mediated through both the TNF-alpha -inducible and the PP-2A-opposing kinases , may serve to target I kappa B alpha for proteasome -mediated degradation .

Together , these results suggest that phosphorylation of <protein>I kappa B alpha</protein> , mediated through both the <protein>TNF-alpha</protein> -inducible and the <protein>PP-2A-opposing kinases</protein> , may serve to target <protein>I kappa B alpha</protein> for <protein>proteasome</protein> -mediated degradation .


Sp1 functions in a chromatin -dependent manner to augment human alpha-globin promoter activity .

<protein>Sp1</protein> functions in a <dna>chromatin</dna> -dependent manner to augment <dna>human alpha-globin promoter</dna> activity .


The 5 ' flanking region of the human alpha-globin gene is highly G + C rich and contains multiple copies of the consensus sequence for the Sp1 binding site .

The <dna>5 ' flanking region</dna> of the <dna>human alpha-globin gene</dna> is highly G + C rich and contains multiple copies of the <dna>consensus sequence</dna> for the <dna>Sp1 binding site</dna> .


We investigated the role of this G + C-rich region in augmenting alpha-globin promoter activity in the presence of the far-upstream alpha-globin enhancer , HS-40 .

We investigated the role of this <dna>G + C-rich region</dna> in augmenting <dna>alpha-globin promoter</dna> activity in the presence of the <dna>far-upstream alpha-globin enhancer</dna> , <dna>HS-40</dna> .


We show that in transiently transfected erythroid cells , deletion of the alpha-globin G + C-rich 5 ' flanking region has no effect on alpha-globin promoter activity .

We show that in <cell_line>transiently transfected erythroid cells</cell_line> , deletion of the <dna>alpha-globin G + C-rich 5 ' flanking region</dna> has no effect on <dna>alpha-globin promoter</dna> activity .


However , upon stable integration into chromatin , deletion of this region causes a nearly 90 % decrease in promoter activity compared with expression from an alpha-globin promoter retaining this region .

However , upon stable integration into <dna>chromatin</dna> , deletion of this region causes a nearly 90 % decrease in promoter activity compared with expression from an <dna>alpha-globin promoter</dna> retaining this region .


These results suggest that the alpha-globin G + C-rich 5 ' flanking region augments alpha-globin promoter activity in a chromatin -dependent manner .

These results suggest that the <dna>alpha-globin G + C-rich 5 ' flanking region</dna> augments <dna>alpha-globin promoter</dna> activity in a <dna>chromatin</dna> -dependent manner .


We further show that this G + C-rich region is required for the activation of alpha-globin gene expression during erythroid differentiation .

We further show that this <dna>G + C-rich region</dna> is required for the activation of <dna>alpha-globin gene</dna> expression during erythroid differentiation .


Finally , we show by both footprint analysis and functional assays that the ability of the G + C-rich region to increase alpha-globin promoter activity from a stably integrated alpha-globin gene is mediated by its multiple binding sites for the transcription factor Sp1 .

Finally , we show by both footprint analysis and functional assays that the ability of the <dna>G + C-rich region</dna> to increase <dna>alpha-globin promoter</dna> activity from a stably integrated <dna>alpha-globin gene</dna> is mediated by its <dna>multiple binding sites</dna> for the <protein>transcription factor</protein> <protein>Sp1</protein> .


Costimulation of human CD4+ T cells with LFA-3 and B7 induce distinct effects on AP-1 and NF-kappa B transcription factors .

Costimulation of <cell_line>human CD4+ T cells</cell_line> with <protein>LFA-3</protein> and <protein>B7</protein> induce distinct effects on AP-1 and <protein>NF-kappa B</protein> <protein>transcription factors</protein> .


We have earlier shown that stimulation of human CD4+ T cells with SEA presented on Chinese hamster ovary ( CHO ) -DR transfectants coexpressing either B7 or LFA-3 resulted in distinct cytokine profiles .

We have earlier shown that stimulation of <cell_line>human CD4+ T cells</cell_line> with SEA presented on <cell_line>Chinese hamster ovary ( CHO ) -DR transfectants</cell_line> coexpressing either <protein>B7</protein> or <protein>LFA-3</protein> resulted in distinct <protein>cytokine</protein> profiles .


We now demonstrate that B7 , but not LFA-3 , strongly costimulated IL-2 transcription and mRNA expression in CD4+ T cells .

We now demonstrate that <protein>B7</protein> , but not <protein>LFA-3</protein> , strongly costimulated <protein>IL-2</protein> transcription and mRNA expression in <cell_line>CD4+ T cells</cell_line> .


Maximal increase in IL-2 transcription was recorded with CHO-DR/B7/LFA-3 , suggesting a cooperative effect of B7 and LFA-3 at the transcriptional level .

Maximal increase in <protein>IL-2</protein> transcription was recorded with <protein>CHO-DR/B7/LFA-3</protein> , suggesting a cooperative effect of <protein>B7</protein> and <protein>LFA-3</protein> at the transcriptional level .


Gel-shift analysis demonstrated that stimulation of CD4+ T cells with CHO-DR and staphylococcal enterotoxin A was sufficient to induce significant amounts of NF-kappa B binding proteins , whereas induction of AP-1 binding proteins required costimulation .

Gel-shift analysis demonstrated that stimulation of <cell_line>CD4+ T cells</cell_line> with <protein>CHO-DR</protein> and staphylococcal enterotoxin A was sufficient to induce significant amounts of <protein>NF-kappa B</protein> binding proteins , whereas induction of <protein>AP-1 binding proteins</protein> required costimulation .


LFA-3 induced moderate levels of AP-1 , but did not influence the levels of NF-kappa B , while B7 costimulation strongly induced both AP-1 and substantially enhanced NF-kappa B binding proteins .

<protein>LFA-3</protein> induced moderate levels of <protein>AP-1</protein> , but did not influence the levels of <protein>NF-kappa B</protein> , while <protein>B7</protein> costimulation strongly induced both <protein>AP-1</protein> and substantially enhanced <protein>NF-kappa B binding proteins</protein> .


The CHO-DR/B7/LFA-3 triple transfectant induced a further increase in AP-1 and NF-kappa B binding proteins compared with the double transfectants .

The <cell_line>CHO-DR/B7/LFA-3 triple transfectant</cell_line> induced a further increase in <protein>AP-1</protein> and <protein>NF-kappa B</protein> <protein>binding proteins</protein> compared with the <cell_line>double transfectants</cell_line> .


The level of Oct-1 binding proteins remained similar in all samples .

The level of <protein>Oct-1 binding proteins</protein> remained similar in all samples .


Super-shift analysis revealed that the NF-kappa B complex of costimulated CD4+ T cells contained large amounts of p50 , substantial amounts of p65 , and marginal levels of c-Rel proteins .

Super-shift analysis revealed that the <protein>NF-kappa B complex</protein> of <cell_line>costimulated CD4+ T cells</cell_line> contained large amounts of <protein>p50</protein> , substantial amounts of <protein>p65</protein> , and marginal levels of <protein>c-Rel proteins</protein> .


The AP-1 binding proteins contained c-Jun , Jun-D , and Fra-1 , but marginal amounts of Jun-B and c-Fos .

The <protein>AP-1 binding proteins</protein> contained <protein>c-Jun</protein> , <protein>Jun-D</protein> , and <protein>Fra-1</protein> , but marginal amounts of <protein>Jun-B</protein> and <protein>c-Fos</protein> .


Our results indicate distinct effects of B7 and LFA-3 costimulation on the activity of AP-1 and NF-kappa B .

Our results indicate distinct effects of <protein>B7</protein> and <protein>LFA-3</protein> costimulation on the activity of <protein>AP-1</protein> and <protein>NF-kappa B</protein> .


These may partly account for the differential effects of B7 and LFA-3 costimulation on IL-2 expression .

These may partly account for the differential effects of <protein>B7</protein> and <protein>LFA-3</protein> costimulation on <protein>IL-2</protein> expression .


The Ah receptor recognizes DNA binding sites for the B cell transcription factor , BSAP : a possible mechanism for dioxin-mediated alteration of CD19 gene expression in human B lymphocytes .

The <protein>Ah receptor</protein> recognizes <dna>DNA binding sites</dna> for the <protein>B cell transcription factor</protein> , <protein>BSAP</protein> : a possible mechanism for dioxin-mediated alteration of <dna>CD19 gene</dna> expression in <cell_type>human B lymphocytes</cell_type> .


2 , 3 , 7 , 8-tetrachlorodibenzo-p-dioxin ( TCDD ) inhibits murine and human B lymphocyte immunoglobulin production through an unknown mechanism .


This study investigated the effect of TCDD on expression of the CD19 gene in a human B lymphocyte cell line .

This study investigated the effect of TCDD on expression of the <dna>CD19 gene</dna> in a <cell_line>human B lymphocyte cell line</cell_line> .


Northern blot analysis showed that TCDD treatment decreased steady state levels of CD19 mRNA by 67 % in the IM-9 cell line .

Northern blot analysis showed that TCDD treatment decreased steady state levels of <rna>CD19 mRNA</rna> by 67 % in the <cell_line>IM-9 cell line</cell_line> .


Using a gel mobility shift assay , we identified a DNA-binding complex in IM-9 nuclear extracts that by several criteria appears to be the Ah receptor .

Using a gel mobility shift assay , we identified a <protein>DNA-binding complex</protein> in IM-9 nuclear extracts that by several criteria appears to be the <protein>Ah receptor</protein> .


In addition , the Ah receptor complex recognized a DNA binding site for B cell lineage-specific activator protein ( BSAP ) in the promoter region of the human CD19 gene which is similar to the consensus Ah receptor DNA binding site .

In addition , the <protein>Ah receptor complex</protein> recognized a <dna>DNA binding site</dna> for <protein>B cell lineage-specific activator protein</protein> ( <protein>BSAP</protein> ) in the <dna>promoter region</dna> of the human <dna>CD19 gene</dna> which is similar to the <dna>consensus Ah receptor DNA binding site</dna> .


These results suggest that the AhR could interfere with BSAP -stimulated CD19 gene transcription by competition for a common DNA binding site .

These results suggest that the <protein>AhR</protein> could interfere with <protein>BSAP</protein> -stimulated <dna>CD19 gene</dna> transcription by competition for a common <dna>DNA binding site</dna> .


Inhibitory action of nm23 proteins on induction of erythroid differentiation of human leukemia cells .

Inhibitory action of <protein>nm23 proteins</protein> on induction of erythroid differentiation of <cell_type>human leukemia cells</cell_type> .


We recently identified a differentiation inhibitory factor ( I-factor ) in mouse myeloid leukemia M1 cells as a murine homolog of the human nm23-H2 gene product .

We recently identified a <protein>differentiation inhibitory factor</protein> ( <protein>I-factor</protein> ) in <cell_line>mouse myeloid leukemia M1 cells</cell_line> as a <protein>murine homolog</protein> of the <protein>human nm23-H2 gene product</protein> .


nm23 genes encode proteins that participate in tumor metastasis regulation and in various fundamental cellular processes , although their mechanisms of action are still unknown .

<dna>nm23 genes</dna> encode proteins that participate in tumor metastasis regulation and in various fundamental cellular processes , although their mechanisms of action are still unknown .


Although all nm23 proteins contain nucleoside diphosphate ( NDP ) kinase activity , it has not been established that the enzyme activity mediated the various functions of nm23 proteins .

Although all <protein>nm23 proteins</protein> contain <protein>nucleoside diphosphate ( NDP ) kinase</protein> activity , it has not been established that the enzyme activity mediated the various functions of <protein>nm23 proteins</protein> .


In the present experiment , we examined the effect of nm23 proteins on various differentiation induction systems of human leukemic cells including HL-60 , U937 , HEL/S , KU812F , K562 , and HEL cells .

In the present experiment , we examined the effect of <protein>nm23 proteins</protein> on various differentiation induction systems of <cell_type>human leukemic cells</cell_type> including <cell_line>HL-60 , U937 , HEL/S , KU812F , K562 , and HEL cells</cell_line> .


Native human erythrocyte NDP kinase protein inhibited the induction of erythroid differentiation of HEL , KU812 and K562 cells , but not the induction of monocytic or granulocytic differentiation of HL-60 , U937 and HEL/S cells .

<protein>Native human erythrocyte NDP kinase protein</protein> inhibited the induction of erythroid differentiation of <cell_line>HEL , KU812 and K562 cells</cell_line> , but not the induction of monocytic or granulocytic differentiation of <cell_line>HL-60 , U937 and HEL/S cells</cell_line> .


The erythroid differentiation of HEL cells was inhibited by recombinant human nm23-H1 , -H2 , mouse nm23-M1 , and -M2 proteins .

The erythroid differentiation of <cell_line>HEL cells</cell_line> was inhibited by <protein>recombinant human nm23-H1 , -H2 , mouse nm23-M1 , and -M2 proteins</protein> .


Moreover , both the mutant nm23-H2His protein and truncated nm23-H2 protein containing N-terminal ( 1-60 ) peptide , which do not have NDP kinase activity , also inhibited erythroid differentiation of HEL cells .

Moreover , both the <protein>mutant nm23-H2His protein</protein> and <protein>truncated nm23-H2 protein</protein> containing <protein>N-terminal ( 1-60 ) peptide</protein> , which do not have <protein>NDP kinase</protein> activity , also inhibited erythroid differentiation of <cell_line>HEL cells</cell_line> .


These results suggest that ( 1 ) the differentiation inhibitory activity of I-factor/nm23 protein is not restricted to monocytic differentiation of M1 cells , ( 2 ) the inhibitory activity is exhibited without species specificity , and ( 3 ) the differentiation inhibitory activity of the nm23/NDP kinase protein is independent of its enzyme activity and requires the presence of N-terminal peptides .

These results suggest that ( 1 ) the differentiation inhibitory activity of <protein>I-factor/nm23 protein</protein> is not restricted to monocytic differentiation of <cell_line>M1 cells</cell_line> , ( 2 ) the inhibitory activity is exhibited without species specificity , and ( 3 ) the differentiation inhibitory activity of the <protein>nm23/NDP kinase protein</protein> is independent of its enzyme activity and requires the presence of N-terminal peptides .


Lipopolysaccharide-induced E-selectin expression requires continuous presence of LPS and is inhibited by bactericidal/permeability-increasing protein .

Lipopolysaccharide-induced <protein>E-selectin</protein> expression requires continuous presence of LPS and is inhibited by <protein>bactericidal/permeability-increasing protein</protein> .


Endothelial cells stimulated by LPS express E-selectin , which plays an important role in mediating neutrophil adhesion during inflammation .

<cell_type>Endothelial cells</cell_type> stimulated by LPS express <protein>E-selectin</protein> , which plays an important role in mediating <cell_type>neutrophil</cell_type> adhesion during inflammation .


E-selectin is induced within 1-2 h , peaks at 4-6 h , and gradually returns to basal level by 24 h .

<protein>E-selectin</protein> is induced within 1-2 h , peaks at 4-6 h , and gradually returns to basal level by 24 h .


rBPI21 , a recombinant N-terminal fragment of human bactericidal/permeability-increasing protein ( BPI ) , inhibited LPS-induced E-selectin expression when added at the same time as , and up to 6 h after , LPS .

<protein>rBPI21</protein> , a <protein>recombinant N-terminal fragment</protein> of <protein>human bactericidal/permeability-increasing protein</protein> ( <protein>BPI</protein> ) , inhibited LPS-induced <protein>E-selectin</protein> expression when added at the same time as , and up to 6 h after , LPS .


Delayed administration of rBPI21 also affected LPS-mediated activation of the nuclear factor , NF-kappa B .

Delayed administration of <protein>rBPI21</protein> also affected LPS-mediated activation of the <protein>nuclear factor</protein> , <protein>NF-kappa B</protein> .


Two to 4 h following LPS addition to endothelial cells , when NF-kappa B was already activated , addition of rBPI21 resulted in marked reduction of NF-kappa B detectable at 4 or 6 h .

Two to 4 h following LPS addition to <cell_type>endothelial cells</cell_type> , when <protein>NF-kappa B</protein> was already activated , addition of <protein>rBPI21</protein> resulted in marked reduction of <protein>NF-kappa B</protein> detectable at 4 or 6 h .


These results indicate that endothelial activation requires continuous presence of LPS , and rBPI21 acts to reverse LPS-mediated endothelial activation by interrupting the on-going LPS signal .

These results indicate that endothelial activation requires continuous presence of LPS , and <protein>rBPI21</protein> acts to reverse LPS-mediated endothelial activation by interrupting the on-going LPS signal .


GM-CSF and IL-2 share common control mechanisms in response to costimulatory signals in T cells .

<protein>GM-CSF</protein> and <protein>IL-2</protein> share common control mechanisms in response to costimulatory signals in <cell_type>T cells</cell_type> .


Antigen complexed with major histocompatibility complex class I or II molecules on the surface of antigen presenting cells interacts with the T cell receptor ( TCR ) on the surface of T cells and initiates an activation cascade .

Antigen complexed with <protein>major histocompatibility complex class I or II molecules</protein> on the surface of <cell_type>antigen presenting cells</cell_type> interacts with the <protein>T cell receptor</protein> ( <protein>TCR</protein> ) on the surface of <cell_type>T cells</cell_type> and initiates an activation cascade .


So called costimulatory signals , mediated by other cell surface interactions or soluble cytokines produced by antigen presenting cells , are also required for complete T cell activation .

So called costimulatory signals , mediated by other cell surface interactions or <protein>soluble cytokines</protein> produced by <cell_type>antigen presenting cells</cell_type> , are also required for complete T cell activation .


High levels of cytokine gene expression in T cells also required both TCR and costimulatory signals .

High levels of <protein>cytokine</protein> gene expression in <cell_type>T cells</cell_type> also required both <protein>TCR</protein> and costimulatory signals .


The granulocyte-macrophage colony-stimulating factor requires sequences in the promoter as well as a powerful enhancer located 3kb upstream to respond to TCR -like signals .

The <protein>granulocyte-macrophage colony-stimulating factor</protein> requires sequences in the <dna>promoter</dna> as well as a powerful <dna>enhancer</dna> located 3kb upstream to respond to <protein>TCR</protein> -like signals .


These promoter and enhancer regions are mainly activated by the transcription factor nuclear factor of activated T cells ( NFAT ) .

These <dna>promoter and enhancer regions</dna> are mainly activated by the <protein>transcription factor nuclear factor of activated T cells</protein> ( <protein>NFAT</protein> ) .


The activation of NFAT by TCR signals has been well described for interleukin-2 ( IL-2 ) and IL-4 gene transcription in T cells .

The activation of <protein>NFAT</protein> by <protein>TCR</protein> signals has been well described for interleukin-2 ( <protein>IL-2</protein> ) and IL-4 gene transcription in <cell_type>T cells</cell_type> .


Costimulatory signals , such as activation of the CD28 cell surface molecule on T cells , lead to activation through a distinct region of the granulocyte-macrophage colony-stimulating factor ( GM-CSF ) promoter .

Costimulatory signals , such as activation of the <protein>CD28 cell surface molecule</protein> on <cell_type>T cells</cell_type> , lead to activation through a distinct region of the <dna>granulocyte-macrophage colony-stimulating factor ( GM-CSF ) promoter</dna> .


This region is termed the CK-1 or CD28RE and appears to bind specific members of the NF-kappa B family of transcription factors .

This region is termed the <dna>CK-1</dna> or <dna>CD28RE</dna> and appears to bind specific members of the <protein>NF-kappa B family</protein> of <protein>transcription factors</protein> .


Human T leukemia virus type 1 ( HTLV-1 ) infects T cells and can lead to increase GM-CSF expression .

Human T leukemia virus type 1 ( HTLV-1 ) infects <cell_type>T cells</cell_type> and can lead to increase <protein>GM-CSF</protein> expression .


We have found that the HTLV-1 transactivator protein , tax , acts as a costimulatory signal for GM-CSF and IL-2 gene transcription , in that it can cooperate with TCR signals to mediate high level gene expression .

We have found that the <protein>HTLV-1 transactivator protein</protein> , <protein>tax</protein> , acts as a costimulatory signal for GM-CSF and IL-2 gene transcription , in that it can cooperate with <protein>TCR</protein> signals to mediate high level gene expression .


Tax activates the GM-CSF promoter through the CK-1 /CD28RE region and also activates nuclear factor-kappa B binding to this region .

Tax activates the <dna>GM-CSF promoter</dna> through the <dna>CK-1</dna> <dna>/CD28RE</dna> region and also activates <protein>nuclear factor-kappa B</protein> binding to this region .


However , other transcription factors or coactivators of NF-kappa B are required for tax activation but these remain to be identified .

However , other <protein>transcription factors</protein> or coactivators of <protein>NF-kappa B</protein> are required for <protein>tax</protein> activation but these remain to be identified .


The CK-1 /CD28RE of GM-CSF shows a high degree of similarity to the IL-2 CD28RE and the IL-3 gene also contains a related region .

The <dna>CK-1</dna> <dna>/CD28RE</dna> of <protein>GM-CSF</protein> shows a high degree of similarity to the <protein>IL-2</protein> <dna>CD28RE</dna> and the <dna>IL-3 gene</dna> also contains a related region .


This observation , together with the fact that both GM-CSF and IL-2 respond to TCR signals via NFAT , implies a high degree of conservation in the regulation of cytokine gene expression in T cells .

This observation , together with the fact that both <protein>GM-CSF</protein> and <protein>IL-2</protein> respond to <protein>TCR</protein> signals via <protein>NFAT</protein> , implies a high degree of conservation in the regulation of <protein>cytokine</protein> gene expression in <cell_type>T cells</cell_type> .


Danazol decreases transcription of estrogen receptor gene in human monocytes .

Danazol decreases transcription of <dna>estrogen receptor gene</dna> in <cell_type>human monocytes</cell_type> .


1. Administration of danazol for over one month reduced the levels of estrogen receptor ( ER ) and its mRNA to approximately 50 and 20 % , respectively in monocytes .

1. Administration of danazol for over one month reduced the levels of <protein>estrogen receptor</protein> ( <protein>ER</protein> ) and its <rna>mRNA</rna> to approximately 50 and 20 % , respectively in <cell_type>monocytes</cell_type> .


2. Danazol did not alter the degradation rate of ER mRNA in monocytes .

2. Danazol did not alter the degradation rate of <rna>ER mRNA</rna> in <cell_type>monocytes</cell_type> .


3. Danazol decreased the transcription rate of ER gene to approximately 50 % in monocytes in a run-on assay .

3. Danazol decreased the transcription rate of <dna>ER gene</dna> to approximately 50 % in <cell_type>monocytes</cell_type> in a run-on assay .


4. Danazol may release estrogen predominance via the reduction of transcription for ER gene , which leads to the reduction of ER mRNA and ER expressions in monocytes .

4. Danazol may release estrogen predominance via the reduction of transcription for <dna>ER gene</dna> , which leads to the reduction of <rna>ER mRNA</rna> and <protein>ER</protein> expressions in <cell_type>monocytes</cell_type> .


Functional characterization of novel IL-2 transcriptional inhibitors .

Functional characterization of novel <protein>IL-2</protein> transcriptional inhibitors .


IL-2 -mediated T cell proliferation is a critical early event in the inflammatory process .

<protein>IL-2</protein> -mediated <cell_type>T cell</cell_type> proliferation is a critical early event in the inflammatory process .


Formation of the NFAT-1 transcriptional complex on the IL-2 promoter is essential for IL-2 transcription .

Formation of the <protein>NFAT-1 transcriptional complex</protein> on the <dna>IL-2 promoter</dna> is essential for <protein>IL-2</protein> transcription .


Using a cell line that is stably transfected with a trimer of the NFAT-1 regulatory element linked to a lac-Z reporter gene , we screened for inhibitors of NFAT -1-mediated beta-galactosidase activity .

Using a cell line that is stably transfected with a trimer of the <dna>NFAT-1 regulatory element</dna> linked to a <dna>lac-Z reporter gene</dna> , we screened for inhibitors of <protein>NFAT</protein> -1-mediated <protein>beta-galactosidase</protein> activity .


WIN 61058 and WIN 53071 were identified as microM inhibitors .


These compounds also inhibited beta-galactosidase mRNA levels .

These compounds also inhibited <rna>beta-galactosidase mRNA</rna> levels .


Similar inhibition of NFAT -1-mediated gene expression was observed in a second cell line , which is stably transfected with NFAT-1 regulatory elements linked to the reporter gene for sCD8 .

Similar inhibition of <protein>NFAT</protein> -1-mediated gene expression was observed in a second <cell_line>cell line</cell_line> , which is stably transfected with <dna>NFAT-1 regulatory elements</dna> linked to the <dna>reporter gene for sCD8</dna> .


At 10 microM , both compounds inhibited IL-2 mRNA and protein levels in the NFAT-1-linked lac-Z transfectants , and in human lymphocytes .

At 10 microM , both compounds inhibited IL-2 mRNA and protein levels in the <cell_line>NFAT-1-linked lac-Z transfectants</cell_line> , and in <cell_type>human lymphocytes</cell_type> .


Both compounds inhibited the mixed lymphocyte reaction , and this inhibition was reversed by exogenous IL-2 .

Both compounds inhibited the mixed lymphocyte reaction , and this inhibition was reversed by exogenous <protein>IL-2</protein> .


WIN 53071 inhibited IL-2 production induced in the calcium-dependent PMA and ionomycin pathway .

WIN 53071 inhibited <protein>IL-2</protein> production induced in the calcium-dependent PMA and ionomycin pathway .


Conversely , calcium-independent anti-CD28 Ab and PMA-induced IL-2 production was resistant .

Conversely , <protein>calcium-independent anti-CD28 Ab</protein> and PMA-induced <protein>IL-2</protein> production was resistant .


Both compounds altered the NFAT-1 transcriptional complex , causing its retarded mobility on gels .

Both compounds altered the <protein>NFAT-1 transcriptional complex</protein> , causing its retarded mobility on gels .


By these functional criteria , we believe we have identified two structurally distinct , novel inhibitors of NFAT -1-mediated transcription .

By these functional criteria , we believe we have identified two structurally distinct , novel inhibitors of <protein>NFAT</protein> -1-mediated transcription .


Transcriptional regulation of the vacuolar H ( + ) -ATPase B2 subunit gene in differentiating THP-1 cells .

Transcriptional regulation of the <dna>vacuolar H ( + ) -ATPase B2 subunit gene</dna> in <cell_line>differentiating THP-1 cells</cell_line> .


Monocyte-macrophage differentiation was used as a model system for studying gene regulation of the human vacuolar H ( + ) -ATPase ( V-ATPase ) .

Monocyte-macrophage differentiation was used as a model system for studying gene regulation of the <protein>human vacuolar H ( + ) -ATPase</protein> ( <protein>V-ATPase</protein> ) .


We examined mRNA levels of various V-ATPase subunits during differentiation of both native monocytes and the cell line THP-1 , and found that transcriptional and post-transcriptional mechanisms could account for increases in cell V-ATPase content .

We examined <rna>mRNA</rna> levels of various <protein>V-ATPase</protein> subunits during differentiation of both <cell_type>native monocytes</cell_type> and the <cell_line>cell line</cell_line> <cell_line>THP-1</cell_line> , and found that transcriptional and post-transcriptional mechanisms could account for increases in cell <protein>V-ATPase</protein> content .


From nuclear runoff experiments , we found that one subunit in particular , the B2 isoform ( Mr = 56 , 000 ) , was amplified primarily by transcriptional means .

From nuclear runoff experiments , we found that one subunit in particular , the <protein>B2 isoform</protein> ( Mr = 56 , 000 ) , was amplified primarily by transcriptional means .


We have begun to examine the structure of the B2 subunit promoter region .

We have begun to examine the structure of the <dna>B2 subunit promoter region</dna> .


Isolation and sequencing of the first exon and 5'-flanking region of this gene reveal a TATA-less promoter with a high G + C content .

Isolation and sequencing of the <dna>first exon</dna> and <dna>5'-flanking region</dna> of this gene reveal a <dna>TATA-less promoter</dna> with a high G + C content .


Primer extension and ribonuclease protection analyses indicate a single major transcriptional start site .

Primer extension and <protein>ribonuclease</protein> protection analyses indicate a single <dna>major transcriptional start site</dna> .


We transfected promoter-luciferase reporter plasmids into THP-1 cells to define sequences that mediate transcriptional control during monocyte differentiation .

We transfected <dna>promoter-luciferase reporter plasmids</dna> into <cell_line>THP-1 cells</cell_line> to define sequences that mediate transcriptional control during monocyte differentiation .


We found that sequences downstream from the transcriptional start site were sufficient to confer increased expression during THP-1 differentiation .

We found that sequences downstream from the transcriptional start site were sufficient to confer increased expression during <cell_line>THP-1</cell_line> differentiation .


DNase I footprinting and sequence analysis revealed the existence of multiple AP2 and Sp1 binding sites in the 5'-untranslated and proximal coding regions .

<protein>DNase I</protein> footprinting and sequence analysis revealed the existence of multiple <dna>AP2 and Sp1 binding sites</dna> in the <dna>5'-untranslated and proximal coding regions</dna> .


Synergy between signal transduction pathways is obligatory for expression of c-fos in B and T cell lines : implication for c-fos control via surface immunoglobulin and T cell antigen receptors .

Synergy between signal transduction pathways is obligatory for expression of <dna>c-fos</dna> in <cell_line>B and T cell lines</cell_line> : implication for <dna>c-fos</dna> control via <protein>surface immunoglobulin</protein> and <protein>T cell antigen receptors</protein> .


Expression of the protooncogene c-fos is controlled by three main regulatory pathways involving kinase C , cAMP , and calcium .

Expression of the <dna>protooncogene c-fos</dna> is controlled by three main regulatory pathways involving <protein>kinase C</protein> , cAMP , and calcium .


Kinase C mediates its effects via phosphorylation of serum response factor ( SRF ) which interacts with the serum response element ( SRE ) ; cAMP and calcium mediate their effects via phosphorylation of CREB ( cAMP regulatory element binding protein ) presumably by activation of a protein kinase A or calmodulin-regulated kinase .

<protein>Kinase C</protein> mediates its effects via phosphorylation of <protein>serum response factor</protein> ( <protein>SRF</protein> ) which interacts with the <dna>serum response element</dna> ( <dna>SRE</dna> ) ; cAMP and calcium mediate their effects via phosphorylation of <protein>CREB</protein> ( <protein>cAMP regulatory element binding protein</protein> ) presumably by activation of a <protein>protein kinase A</protein> or <protein>calmodulin-regulated kinase</protein> .


We have examined the function of these elements in Burkitt 's lymphoma cells ( Ramos and Daudi ) as well as a T lymphocytic cell line ( Jurkat ) .

We have examined the function of these elements in <cell_line>Burkitt 's lymphoma cells</cell_line> ( <cell_line>Ramos</cell_line> and <cell_line>Daudi</cell_line> ) as well as a <cell_line>T lymphocytic cell line</cell_line> ( <cell_line>Jurkat</cell_line> ) .


We have found that stimulation of any one of these pathways alone has little or no effect on c-fos induction .

We have found that stimulation of any one of these pathways alone has little or no effect on <dna>c-fos</dna> induction .


However , kinase C activation ( PMA stimulation ) combined with either cAMP ( forskolin plus MIX ) or calcium stimulation ( ionophore ) leads to greatly enhanced c-fos induction .

However , <protein>kinase C</protein> activation ( PMA stimulation ) combined with either cAMP ( forskolin plus MIX ) or calcium stimulation ( ionophore ) leads to greatly enhanced <dna>c-fos</dna> induction .


By contrast , cAMP in the presence of calcium shows no synergy in c-fos induction .

By contrast , cAMP in the presence of calcium shows no synergy in <dna>c-fos</dna> induction .


Okadaic acid augments PMA- as well as calcium-mediated activation of c-fos , and has little or no effect when combined with cAMP .

Okadaic acid augments PMA- as well as calcium-mediated activation of <dna>c-fos</dna> , and has little or no effect when combined with cAMP .


The main difference between Ramos ( B cells ) and Jurkat ( T cells ) in the regulation of c-fos is that cAMP plus calcium is strongly synergistic in Jurkat and is without effect in Ramos .

The main difference between <cell_line>Ramos</cell_line> ( <cell_type>B cells</cell_type> ) and <cell_line>Jurkat</cell_line> ( <cell_type>T cells</cell_type> ) in the regulation of <dna>c-fos</dna> is that cAMP plus calcium is strongly synergistic in <cell_line>Jurkat</cell_line> and is without effect in <cell_line>Ramos</cell_line> .


Analysis of AP-1 activity using gel mobility shift assays confirms that the requirements for synergy in c-fos mRNA induction are paralleled by requirements for synergy in induction of AP-1 activity .

Analysis of <protein>AP-1</protein> activity using gel mobility shift assays confirms that the requirements for synergy in <rna>c-fos mRNA</rna> induction are paralleled by requirements for synergy in induction of <protein>AP-1</protein> activity .


Signaling in B cells due to anti-Ig stimulation involves both kinase C activation and release of intracellular calcium , and results in c-fos mRNA induction .

Signaling in <cell_type>B cells</cell_type> due to <protein>anti-Ig</protein> stimulation involves both <protein>kinase C</protein> activation and release of intracellular calcium , and results in <rna>c-fos mRNA</rna> induction .


Our results indicate that synergy between the kinase C activation and calcium is needed for efficient c-fos induction since neither of these two alone induces c-fos well .

Our results indicate that synergy between the <protein>kinase C</protein> activation and calcium is needed for efficient <dna>c-fos</dna> induction since neither of these two alone induces <dna>c-fos</dna> well .


That synergy of signaling pathways is relevant for the anti-Ig induction of c-fos is supported by the fact that cAMP-inducing agents and okadaic acid further enhance anti-Ig induction of c-fos .

That synergy of signaling pathways is relevant for the <protein>anti-Ig</protein> induction of <dna>c-fos</dna> is supported by the fact that cAMP-inducing agents and okadaic acid further enhance <protein>anti-Ig</protein> induction of <dna>c-fos</dna> .


These results suggest that cell-specific patterns of synergy are an essential feature for c-fos induction and may be relevant for c-fos control through B and T cell antigen receptors .

These results suggest that cell-specific patterns of synergy are an essential feature for <dna>c-fos</dna> induction and may be relevant for <dna>c-fos</dna> control through <protein>B and T cell antigen receptors</protein> .


Multiple signals are required for function of the human granulocyte-macrophage colony-stimulating factor gene promoter in T cells .

Multiple signals are required for function of the <dna>human granulocyte-macrophage colony-stimulating factor gene promoter</dna> in <cell_type>T cells</cell_type> .


The human granulocyte-macrophage CSF ( GM-CSF ) gene is expressed in T cells in response to TCR activation that can be mimicked by treatment of the cells with PMA and Ca2+ ionophore .

The <dna>human granulocyte-macrophage CSF ( GM-CSF ) gene</dna> is expressed in <cell_type>T cells</cell_type> in response to <protein>TCR</protein> activation that can be mimicked by treatment of the cells with PMA and Ca2+ ionophore .


The gene contains a proximal functional promoter region ( -620 to +34 ) , as well as a powerful enhancer located 3 kb upstream , both of which are involved in the response of the gene to TCR activation .

The gene contains a <dna>proximal functional promoter region</dna> ( <dna>-620 to +34</dna> ) , as well as a powerful <dna>enhancer</dna> located 3 kb upstream , both of which are involved in the response of the gene to <protein>TCR</protein> activation .


The proximal promoter contains a region termed CLEO ( -54 to -31 ) that consists of a purine-rich element abutting an activator protein-1 ( AP-1 ) -like site , as well as an upstream nuclear factor-kappa B ( NF-kappa B ) site ( -85 to -76 ) and a CK-1 element ( -101 to -92 ) .

The <dna>proximal promoter</dna> contains a region termed <dna>CLEO</dna> ( <dna>-54 to -31</dna> ) that consists of a <dna>purine-rich element</dna> abutting an <dna>activator protein-1 ( AP-1 ) -like site</dna> , as well as an <dna>upstream nuclear factor-kappa B ( NF-kappa B ) site</dna> ( <dna>-85 to -76</dna> ) and a <dna>CK-1 element</dna> ( <dna>-101 to -92</dna> ) .


We show in this work that mutations in either the purine-rich region of the CLEO element or the NF-kappa B site result in reduced PMA/Ca2+ activation of a 620-bp human GM-CSF promoter-luciferase reporter construct in Jurkat T cells by 65 % and 50 % , respectively .

We show in this work that mutations in either the <dna>purine-rich region</dna> of the <dna>CLEO element</dna> or the <dna>NF-kappa B site</dna> result in reduced PMA/Ca2+ activation of a <dna>620-bp human GM-CSF promoter-luciferase reporter construct</dna> in <cell_line>Jurkat T cells</cell_line> by 65 % and 50 % , respectively .


The major inducible protein complex that binds to the human CLEO ( hCLEO ) element is an AP-1-like complex that is inducible by PMA alone , but shows increased binding in response to PMA together with Ca2+ ionophore .

The major <protein>inducible protein complex</protein> that binds to the <dna>human CLEO ( hCLEO ) element</dna> is an <protein>AP-1-like complex</protein> that is inducible by PMA alone , but shows increased binding in response to PMA together with Ca2+ ionophore .


Although the binding of this complex is not cyclosporin-sensitive , promoter induction is inhibited by cyclosporin treatment .


A second weak inducible complex resembling nuclear factor of activated T cells ( NF-AT ) was also observed binding to the hCLEO region .

A second weak inducible complex resembling <protein>nuclear factor of activated T cells</protein> ( <protein>NF-AT</protein> ) was also observed binding to the <dna>hCLEO region</dna> .


By using recombinant proteins , we confirmed that AP-1 , NF-ATp , and a higher order NF-ATp/AP-1 complex could all form with the hCLEO element , and we have also defined the sequence requirements for binding of each of these complexes .

By using <protein>recombinant proteins</protein> , we confirmed that <protein>AP-1</protein> , <protein>NF-ATp</protein> , and a higher order <protein>NF-ATp/AP-1 complex</protein> could all form with the <dna>hCLEO element</dna> , and we have also defined the sequence requirements for binding of each of these complexes .


We found that expression of a constitutively active form of calcineurin could substitute for Ca2+ ionophore and synergize with PMA to activate the GM-CSF promoter , and conversely that mutant-activated Ras could substitute for PMA and cooperate with Ca2+ ionophore .

We found that expression of a constitutively active form of <protein>calcineurin</protein> could substitute for Ca2+ ionophore and synergize with PMA to activate the <dna>GM-CSF promoter</dna> , and conversely that <protein>mutant-activated Ras</protein> could substitute for PMA and cooperate with Ca2+ ionophore .


Co-expression of Ras and calcineurin , however , did not activate the GM-CSF promoter , but required the additional expression of NF-kappa B p65 .

Co-expression of <protein>Ras</protein> and <protein>calcineurin</protein> , however , did not activate the <dna>GM-CSF promoter</dna> , but required the additional expression of <protein>NF-kappa B p65</protein> .


These results imply that at least three signals are required to activate the GM-CSF proximal promoter , and that the signals impinge on distinct transcription factors that bind to the hCLEO and NF-kappa B regions of the promoter .

These results imply that at least three signals are required to activate the <dna>GM-CSF proximal promoter</dna> , and that the signals impinge on distinct <protein>transcription factors</protein> that bind to the <dna>hCLEO and NF-kappa B regions</dna> of the <dna>promoter</dna> .


IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes .

IL-10 induces the tyrosine phosphorylation of <protein>tyk2</protein> and <protein>Jak1</protein> and the differential assembly of <protein>STAT1 alpha</protein> and <protein>STAT3 complexes</protein> in <cell_type>human T cells</cell_type> and <cell_type>monocytes</cell_type> .


IL-10 affects monocytes and T cells by driving the progression of immune responsiveness such that Th2 lymphocyte-mediated effects predominate .

<protein>IL-10</protein> affects <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> by driving the progression of immune responsiveness such that Th2 lymphocyte-mediated effects predominate .


In this report , we show that in monocytes and T cells IL-10 stimulates tyrosine phosphorylation of the signal transducers and activators of transcription , STAT1 alpha and STAT3 , in a differential manner such that the relative formation of homo- and heterodimers varies between the two cell types .

In this report , we show that in <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> <protein>IL-10</protein> stimulates tyrosine phosphorylation of the <protein>signal transducers</protein> and <protein>activators of transcription</protein> , <protein>STAT1 alpha</protein> and <protein>STAT3</protein> , in a differential manner such that the relative formation of <protein>homo- and heterodimers</protein> varies between the two cell types .


Moreover , monocytes express a novel IL-10-stimulated STAT protein with an M ( r ) of 70 kDa that is recognized by the anti-STAT3 Ab but is not observed in T cells .

Moreover , <cell_type>monocytes</cell_type> express a novel <protein>IL-10-stimulated STAT protein</protein> with an M ( r ) of <protein>70 kDa</protein> that is recognized by the <protein>anti-STAT3 Ab</protein> but is not observed in <cell_type>T cells</cell_type> .


IL-10 treatment of both T cells and monocytes results in the ligand-induced tyrosine phosphorylation of tyk2 and Jak1 , but not Jak2 or Jak3 .

<protein>IL-10</protein> treatment of both <cell_type>T cells</cell_type> and <cell_type>monocytes</cell_type> results in the ligand-induced tyrosine phosphorylation of <protein>tyk2</protein> and <protein>Jak1</protein> , but not <protein>Jak2</protein> or <protein>Jak3</protein> .


Selective modulation of immune responsiveness by IL-10 in cells such as monocytes and T cells may result in part from the differential activation of STAT protein pairs .

Selective modulation of immune responsiveness by <protein>IL-10</protein> in cells such as <cell_type>monocytes</cell_type> and <cell_type>T cells</cell_type> may result in part from the differential activation of <protein>STAT protein pairs</protein> .


Use of new biologic markers in the ovulation induction .


Biological markers of ovulation , after a great in the past , have been fallen into disuse for the large diffusion of biochemical and biophysical ones .


However , the real effect of hormones involved in ovulation is expressed by biological modifications on target tissues .

However , the real effect of hormones involved in ovulation is expressed by biological modifications on <cell_type>target tissues</cell_type> .


To explore the modifications of not reproductive target tissues as ovulation markers we studied the behaviour of Albuminemia , Platelet Factor IV ( as indicator of Platelet Aggregation ) , Type II estrogenic receptors in 42 ovulation induced women , undergoing our observation .

To explore the modifications of not reproductive target tissues as ovulation markers we studied the behaviour of Albuminemia , <protein>Platelet Factor IV</protein> ( as indicator of Platelet Aggregation ) , <protein>Type II estrogenic receptors</protein> in 42 ovulation induced women , undergoing our observation .


33 of them had ovulation and 9 developed a LUF syndrome , constituting two biological models of an opposite situation for the three markers observed .


All the markers considered were sufficiently sensitive , but among them , Platelet Factor IV was the most reliable to the hormonal ovulatory situation .

All the markers considered were sufficiently sensitive , but among them , <protein>Platelet Factor IV</protein> was the most reliable to the hormonal ovulatory situation .


Abnormal regulation of the IL-2 promoter in lpr CD4-CD8- T lymphocytes results in constitutive expression of a novel nuclear factor of activated T cells-binding factor .

Abnormal regulation of the <dna>IL-2 promoter</dna> in lpr <cell_line>CD4-CD8- T lymphocytes</cell_line> results in constitutive expression of a <protein>novel nuclear factor of activated T cells-binding factor</protein> .


The inert quality of MRL-Ipr/Ipr ( Ipr ) peripheral CD4-CD8- ( CD4-8- ) T cells manifests primarily as an inability to proliferate or produce IL-2 in response to TCR or mitogenic stimulation .

The inert quality of <cell_line>MRL-Ipr/Ipr ( Ipr ) peripheral CD4-CD8- ( CD4-8- ) T cells</cell_line> manifests primarily as an inability to proliferate or produce <protein>IL-2</protein> in response to <protein>TCR</protein> or mitogenic stimulation .


Yet these same cells do initiate early TCR -mediated signaling events , such as generation of inositol phosphates and increased intracellular calcium .

Yet these same cells do initiate early <protein>TCR</protein> -mediated signaling events , such as generation of inositol phosphates and increased intracellular calcium .


They also display constitutively high levels of p59fyn and CD3 zeta tyrosine phosphorylation .

They also display constitutively high levels of <protein>p59fyn</protein> and <protein>CD3 zeta</protein> tyrosine phosphorylation .


The generation of second messengers in T cells normally leads to downstream signaling that results in transcriptional activation of the IL-2 gene .

The generation of second messengers in <cell_type>T cells</cell_type> normally leads to downstream signaling that results in transcriptional activation of the <dna>IL-2 gene</dna> .


We , therefore , compared the activation state of the IL-2 gene promoter region in freshly isolated and stimulated Ipr CD4-8- T cells with that of normal T lymphocytes .

We , therefore , compared the activation state of the <dna>IL-2 gene promoter region</dna> in freshly isolated and stimulated <cell_line>Ipr CD4-8- T cells</cell_line> with that of <cell_type>normal T lymphocytes</cell_type> .


Levels of the octamer , NF-kappa B ( p50-p65 heterodimer ) , and AP-1 transcriptional factors are constitutively elevated in freshly isolated Ipr CD4-8- T cells , consistent with the activated phenotype of these cells .

Levels of the octamer , <protein>NF-kappa B</protein> ( <protein>p50-p65 heterodimer</protein> ) , and <protein>AP-1 transcriptional factors</protein> are constitutively elevated in freshly isolated <cell_line>Ipr CD4-8- T cells</cell_line> , consistent with the activated phenotype of these cells .


Upon stimulation with mitogens , formation of the transactivating complex , nuclear factor of activated T cells ( NF-AT ) , occurs with normal kinetics in Ipr CD4-8- T cells .

Upon stimulation with mitogens , formation of the transactivating complex , <protein>nuclear factor of activated T cells</protein> ( <protein>NF-AT</protein> ) , occurs with normal kinetics in <cell_line>Ipr CD4-8- T cells</cell_line> .


Yet , the levels of the activating NF-AT complex never reach those observed in similarly stimulated normal T cells .

Yet , the levels of the activating <protein>NF-AT complex</protein> never reach those observed in similarly stimulated normal <cell_type>T cells</cell_type> .


Furthermore , nuclear extracts from Ipr CD4-8- T cells display high levels of a novel specific binding activity at the NF-AT site , which is present at much lower levels in freshly isolated normal T lymphocytes .

Furthermore , nuclear extracts from <cell_line>Ipr CD4-8- T cells</cell_line> display high levels of a novel specific binding activity at the <dna>NF-AT site</dna> , which is present at much lower levels in freshly isolated <cell_type>normal T lymphocytes</cell_type> .


Upon mitogenic stimulation , the binding activity of the novel NF-AT-binding factor is rapidly down-regulated in normal T cells , but persists at high levels in Ipr CD4-8- T cells .

Upon mitogenic stimulation , the binding activity of the novel <protein>NF-AT-binding factor</protein> is rapidly down-regulated in normal <cell_type>T cells</cell_type> , but persists at high levels in <cell_line>Ipr CD4-8- T cells</cell_line> .


These two abnormalities at the NF-AT site provide a potential mechanism to account for the defect in IL-2 production from Ipr CD4-8- T cells .

These two abnormalities at the <dna>NF-AT site</dna> provide a potential mechanism to account for the defect in <protein>IL-2</protein> production from <cell_line>Ipr CD4-8- T cells</cell_line> .


Cross-linking of CD30 induces HIV expression in chronically infected T cells .

Cross-linking of <protein>CD30</protein> induces HIV expression in chronically infected <cell_type>T cells</cell_type> .


CD30 , a member of the tumor necrosis factor ( TNF ) receptor family , is expressed constitutively on the surface of the human T cell line ACH-2 , which is chronically infected with human immunodeficiency virus type-1 ( HIV ) -1 .

<protein>CD30</protein> , a member of the tumor necrosis factor ( TNF ) receptor family , is expressed constitutively on the surface of the human T cell line ACH-2 , which is chronically infected with human immunodeficiency virus type-1 ( HIV ) -1 .


We demonstrate that cross-linking CD30 with an anti- CD30 -specific monoclonal antibody , which mimics the described biological activities of the CD30 ligand ( CD30L ) , results in HIV expression .

We demonstrate that cross-linking <protein>CD30</protein> with an anti- <protein>CD30</protein> -specific monoclonal antibody , which mimics the described biological activities of the <protein>CD30 ligand</protein> ( <protein>CD30L</protein> ) , results in HIV expression .


CD30 cross-linking does not alter proliferation of ACH-2 cells and the induction of HIV expression is not mediated by endogenous TNF alpha/beta .

<protein>CD30</protein> cross-linking does not alter proliferation of <cell_line>ACH-2 cells</cell_line> and the induction of HIV expression is not mediated by endogenous <protein>TNF alpha/beta</protein> .


Furthermore , cross-linking of CD30 leads to NF-kappa B activation and enhanced HIV transcription .

Furthermore , cross-linking of <protein>CD30</protein> leads to <protein>NF-kappa B</protein> activation and enhanced HIV transcription .


Thus , CD30 -CD30L interactions mediate the induction of HIV expression by a kappa B-dependent pathway that is independent of TNF .

Thus , <protein>CD30</protein> <protein>-CD30L</protein> interactions mediate the induction of HIV expression by a kappa B-dependent pathway that is independent of <protein>TNF</protein> .


This mechanism may be important in the activation of HIV expression from latently infected CD4+ T cells , especially in lymphoid organs where cell to cell contact is conducive to receptor-ligand interactions .

This mechanism may be important in the activation of HIV expression from latently infected <cell_line>CD4+ T cells</cell_line> , especially in lymphoid organs where cell to cell contact is conducive to receptor-ligand interactions .


Human MHC class II gene transcription directed by the carboxyl terminus of CIITA , one of the defective genes in type II MHC combined immune deficiency .

Human <dna>MHC class II gene</dna> transcription directed by the <protein>carboxyl terminus</protein> of <dna>CIITA</dna> , one of the <dna>defective genes</dna> in type II <protein>MHC</protein> combined immune deficiency .


Type II major histocompatibility complex combined immune deficiency ( type II MHC CID or bare lymphocyte syndrome ) is a congenital immunodeficiency disease characterized by absent MHC class II expression .

<protein>Type II major histocompatibility complex</protein> combined immune deficiency ( type II <protein>MHC</protein> CID or bare lymphocyte syndrome ) is a congenital immunodeficiency disease characterized by absent <protein>MHC class II</protein> expression .


Four distinct complementation groups have been identified .


Recently , the defective gene in group II type II MHC CID has been isolated and termed CIITA .

Recently , the <dna>defective gene</dna> in group II type II <protein>MHC</protein> CID has been isolated and termed <dna>CIITA</dna> .


Here , we demonstrate that CIITA is an MHC class II gene-specific transcription activator .

Here , we demonstrate that <dna>CIITA</dna> is an <dna>MHC class II gene-specific transcription activator</dna> .


The transcription activation function is provided by the N-terminal acidic domain ( amino acids 26-137 ) , which is experimentally exchangeable with a heterologous viral transcription-activating domain .

The transcription activation function is provided by the <protein>N-terminal acidic domain</protein> ( <protein>amino acids 26-137</protein> ) , which is experimentally exchangeable with a <protein>heterologous viral transcription-activating domain</protein> .


The specificity of CIITA for three major MHC class II genes , DR , DQ and DP , is mediated by its remaining C-terminal residues ( amino acids 317-1130 ) .

The specificity of <protein>CIITA</protein> for three major <dna>MHC class II genes</dna> , <dna>DR</dna> , <dna>DQ</dna> and <dna>DP</dna> , is mediated by its remaining <protein>C-terminal residues</protein> ( <protein>amino acids 317-1130</protein> ) .


The transactivation of multiple cis elements , especially S and X2 , of the DR alpha proximal promoter in group II CID cells is CIITA dependent .

The transactivation of <dna>multiple cis elements</dna> , especially <dna>S</dna> and <dna>X2</dna> , of the <dna>DR alpha proximal promoter</dna> in <cell_line>group II CID cells</cell_line> is <protein>CIITA</protein> dependent .


Since CIITA overexpression in normal cells did not increase class II expression , we propose that initiation of CIITA expression serves as the on-off switch , while availability of downstream interactor ( s ) limits transcription .

Since <protein>CIITA</protein> overexpression in <cell_type>normal cells</cell_type> did not increase class II expression , we propose that initiation of <protein>CIITA</protein> expression serves as the on-off switch , while availability of downstream interactor ( s ) limits transcription .


Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion .

Monocyte tethering by <protein>P-selectin</protein> regulates <protein>monocyte chemotactic protein-1</protein> and <protein>tumor necrosis factor-alpha</protein> secretion .


Signal integration and NF-kappa B translocation [ see comments ]

Signal integration and <protein>NF-kappa B</protein> translocation [ see comments ]


Adhesion molecules that tether circulating leukocytes to endothelial cells may also transduce or modulate outside-in signals for cellular activation , providing an initial regulatory point in the inflammatory response .

<protein>Adhesion molecules</protein> that tether <cell_type>circulating leukocytes</cell_type> to <cell_type>endothelial cells</cell_type> may also transduce or modulate outside-in signals for cellular activation , providing an initial regulatory point in the inflammatory response .


Adhesion of human monocytes to P-selectin , the most rapidly expressed endothelial tethering factor , increased the secretion of monocyte chemotactic protein-1 ( MCP-1 ) and tumor necrosis factor-alpha ( TNF-alpha ) by the leukocytes when they were stimulated with platelet-activating factor .

Adhesion of <cell_type>human monocytes</cell_type> to <protein>P-selectin</protein> , the most rapidly expressed <protein>endothelial tethering factor</protein> , increased the secretion of <protein>monocyte chemotactic protein-1</protein> ( <protein>MCP-1</protein> ) and <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) by the <cell_type>leukocytes</cell_type> when they were stimulated with <protein>platelet-activating factor</protein> .


Increased cytokine secretion was specifically inhibited by G1 , an anti-P-selectin mAb that prevents P-selectin from binding to its ligand ( P-selectin glycoprotein ligand-1 ) on myeloid cells .

Increased cytokine secretion was specifically inhibited by <protein>G1</protein> , an <protein>anti-P-selectin mAb</protein> that prevents <protein>P-selectin</protein> from binding to its ligand ( <protein>P-selectin glycoprotein ligand-1</protein> ) on <cell_type>myeloid cells</cell_type> .


Moreover , tethering by P-selectin specifically enhanced nuclear translocation of nuclear factor-kappa B ( NF-kappa B ) , a transcription factor required for expression of MCP-1 , TNF-alpha , and other immediate-early genes .

Moreover , tethering by <protein>P-selectin</protein> specifically enhanced nuclear translocation of <protein>nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) , a <protein>transcription factor</protein> required for expression of <protein>MCP-1</protein> , <protein>TNF-alpha</protein> , and other <dna>immediate-early genes</dna> .


These results demonstrate that P-selectin , through its ligands on monocytes , may locally regulate cytokine secretion in inflamed tissues .

These results demonstrate that <protein>P-selectin</protein> , through its ligands on <cell_type>monocytes</cell_type> , may locally regulate <protein>cytokine</protein> secretion in inflamed tissues .


Functional roles of in vivo footprinted DNA motifs within an alpha-globin enhancer .

Functional roles of <dna>in vivo footprinted DNA motifs</dna> within an <dna>alpha-globin enhancer</dna> .


Erythroid lineage and developmental stage specificities .


Transcriptional regulation of the human alpha-like globin genes , embryonic zeta 2 and adult alpha , during erythroid development is mediated by a distal enhancer , HS-40 .

Transcriptional regulation of the <dna>human alpha-like globin genes</dna> , <dna>embryonic zeta 2</dna> and <dna>adult alpha</dna> , during erythroid development is mediated by a <dna>distal enhancer</dna> , <dna>HS-40</dna> .


Previous protein-DNA binding studies have shown that HS-40 consists of multiple nuclear factor binding motifs that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner .

Previous protein-DNA binding studies have shown that <dna>HS-40</dna> consists of multiple <dna>nuclear factor binding motifs</dna> that are occupied in vivo in an erythroid lineage- and developmental stage-specific manner .


We have systematically analyzed the functional roles of these factor binding motifs of HS-40 by site-directed mutagenesis and transient expression assay in erythroid cell cultures .

We have systematically analyzed the functional roles of these <dna>factor binding motifs</dna> of <dna>HS-40</dna> by site-directed mutagenesis and transient expression assay in <cell_line>erythroid cell cultures</cell_line> .


Three of these HS-40 enhancer motifs , 5'NF-E2/AP1 , GT II , and GATA-1 ( c ) , positively regulate the zeta 2-globin promoter activity in embryonic/fetal erythroid K562 cells and the adult alpha-globin promoter activity in adult erythroid MEL cells .

Three of these <dna>HS-40 enhancer motifs</dna> , <dna>5'NF-E2/AP1</dna> , <dna>GT II</dna> , and <dna>GATA-1 ( c )</dna> , positively regulate the <dna>zeta 2-globin promoter</dna> activity in <cell_line>embryonic/fetal erythroid K562 cells</cell_line> and the <dna>adult alpha-globin promoter</dna> activity in <cell_line>adult erythroid MEL cells</cell_line> .


On the other hand , the 3'NF-E2/AP1 motif is able to exert both positive and negative regulatory effects on the zeta 2-globin promoter activity in K562 cells , and this dual function appears to be modulated through differential binding of the ubiquitous AP1 factors and the erythroid-enriched NF-E2 factor .

On the other hand , the <dna>3'NF-E2/AP1 motif</dna> is able to exert both positive and negative regulatory effects on the <dna>zeta 2-globin promoter</dna> activity in <cell_line>K562 cells</cell_line> , and this dual function appears to be modulated through differential binding of the <protein>ubiquitous AP1 factors</protein> and the <protein>erythroid-enriched NF-E2 factor</protein> .


Mutation in the GATA-1 ( d ) motif , which exhibits an adult erythroid-specific genomic footprint , decreases the HS-40 enhancer function in dimethyl sulfoxide-induced MEL cells but not in K562 cells .

Mutation in the <dna>GATA-1 ( d ) motif</dna> , which exhibits an <dna>adult erythroid-specific genomic footprint</dna> , decreases the <dna>HS-40 enhancer</dna> function in <cell_line>dimethyl sulfoxide-induced MEL cells</cell_line> but not in <cell_line>K562 cells</cell_line> .


These studies have defined the regulatory roles of the different HS-40 motifs .

These studies have defined the regulatory roles of the different <dna>HS-40 motifs</dna> .