Atopy , which predisposes individuals to develop asthma , severe systemic anaphylaxis , and atopic dermatitis , is usually associated with dramatically elevated total serum IgE levels and is thought to be controlled by a major susceptibility gene and multiple minor susceptibility genes .

Atopy , which predisposes individuals to develop asthma , severe systemic anaphylaxis , and atopic dermatitis , is usually associated with dramatically elevated total serum <protein>IgE</protein> levels and is thought to be controlled by a major <dna>susceptibility gene</dna> and multiple minor <dna>susceptibility genes</dna> .


A recent sib-pair analysis revealed a tight linkage between markers on 5q31.1 and a major susceptibility gene controlling total serum IgE levels .

A recent sib-pair analysis revealed a tight linkage between markers on <dna>5q31.1</dna> and a <dna>major susceptibility gene</dna> controlling total serum <protein>IgE</protein> levels .


Due to its location within this cluster and its biologic role in Ig class switching and Th2 cell differentiation , the IL-4 gene has emerged as one major candidate for the atopy gene .

Due to its location within this cluster and its biologic role in Ig class switching and <cell_line>Th2 cell</cell_line> differentiation , the <dna>IL-4 gene</dna> has emerged as one major candidate for the <dna>atopy gene</dna> .


In one model , polymorphisms within IL-4 regulatory elements might result in overexpression of the gene , amplifying Th2 cell differentiation and class switching to IgE .

In one model , polymorphisms within <dna>IL-4 regulatory elements</dna> might result in overexpression of the gene , amplifying <cell_line>Th2 cell</cell_line> differentiation and class switching to <protein>IgE</protein> .


In support of this model , we report that the human IL-4 promoter exists in multiple allelic forms that exhibit distinct transcriptional activities in IL-4-positive T cells .

In support of this model , we report that the <dna>human IL-4 promoter</dna> exists in multiple allelic forms that exhibit distinct transcriptional activities in <cell_type>IL-4-positive T cells</cell_type> .


A particular allele has an unusually high transcriptional activity .


A nucleotide substitution within a recently described OAP40 element located just upstream of an NF-AT site ( P sequence ) appears to be largely responsible for the increased promotor strength of this particular allelic form of the IL-4 promoter .

A nucleotide substitution within a recently described <dna>OAP40 element</dna> located just upstream of an <dna>NF-AT site</dna> ( <dna>P sequence</dna> ) appears to be largely responsible for the increased promotor strength of this particular allelic form of the <dna>IL-4 promoter</dna> .


In EMSAs , this substitution results in a markedly enhanced affinity for sequence-specific complexes exhibiting an AP-1 specificity .

In EMSAs , this substitution results in a markedly enhanced affinity for sequence-specific complexes exhibiting an <protein>AP-1</protein> specificity .


The identification of allelic nucleotides , which results in overexpression of the IL-4 gene , provides specific targets for a comprehensive screening of atopic and nonatopic individuals and may provide a clue for genetic predisposition for atopy .

The identification of allelic nucleotides , which results in overexpression of the <dna>IL-4 gene</dna> , provides specific targets for a comprehensive screening of atopic and nonatopic individuals and may provide a clue for genetic predisposition for atopy .


Evidence for lowered induction of nuclear factor kappa B in activated human T lymphocytes during aging .

Evidence for lowered induction of <protein>nuclear factor kappa B</protein> in <cell_type>activated human T lymphocytes</cell_type> during aging .


Transcription factor NF kappa B ( nuclear factor kappa B ) is induced in T lymphocytes from young individuals following activation with a variety of stimuli including anti-CD3 , phorbol myristate acetate ( PMA ) , and tumor necrosis factor-alpha ( TNF-alpha ) .

Transcription factor <protein>NF kappa B</protein> ( <protein>nuclear factor kappa B</protein> ) is induced in <cell_type>T lymphocytes</cell_type> from young individuals following activation with a variety of stimuli including <protein>anti-CD3</protein> , phorbol myristate acetate ( PMA ) , and <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) .


In contrast , activated T lymphocytes from older individuals show a significant reduction in the induction of NF kappa B in response to the same stimuli .

In contrast , activated <cell_type>T lymphocytes</cell_type> from older individuals show a significant reduction in the induction of <protein>NF kappa B</protein> in response to the same stimuli .


The age-related decline in induction of NF kappa B could not be attributed to alteration in the composition of subunits , p50 and p65 were found to be the predominant subunits of induced NF kappa B in T cells from young as well as elderly donors .

The age-related decline in induction of <protein>NF kappa B</protein> could not be attributed to alteration in the composition of subunits , <protein>p50</protein> and <protein>p65</protein> were found to be the predominant subunits of induced <protein>NF kappa B</protein> in <cell_type>T cells</cell_type> from young as well as elderly donors .


Furthermore , similar levels of NF kappa B were found in the cytosols of unactivated T cells from both young and elderly donors suggesting that precursor levels of NF kappa B remain unaltered during aging .

Furthermore , similar levels of <protein>NF kappa B</protein> were found in the cytosols of unactivated <cell_type>T cells</cell_type> from both young and elderly donors suggesting that precursor levels of <protein>NF kappa B</protein> remain unaltered during aging .


These results suggest that an age-associated decline in the induction of NF kappa B in activated T cells from elderly individuals may be attributable to altered regulation of the inhibitor , I kappa B , and may play an important role in immune dysregulation accompanying aging .

These results suggest that an age-associated decline in the induction of <protein>NF kappa B</protein> in activated <cell_type>T cells</cell_type> from elderly individuals may be attributable to altered regulation of the inhibitor , <protein>I kappa B</protein> , and may play an important role in immune dysregulation accompanying aging .


Inhibition of lipopolysaccharide-induced monocyte interleukin-1 receptor antagonist synthesis by cortisol : involvement of the mineralocorticoid receptor .

Inhibition of lipopolysaccharide-induced <protein>monocyte interleukin-1 receptor</protein> antagonist synthesis by cortisol : involvement of the <protein>mineralocorticoid receptor</protein> .


Glucocorticoids , as a part of their physiological role in the control of inflammatory and immune processes , suppress the expression of interleukin-1 ( IL-1 ) and other cytokines .

Glucocorticoids , as a part of their physiological role in the control of inflammatory and immune processes , suppress the expression of <protein>interleukin-1</protein> ( <protein>IL-1</protein> ) and other <protein>cytokines</protein> .


Human monocyte IL-1 receptor antagonist ( IL-1ra ) messenger ribonucleic acid ( mRNA ) expression and protein secretion are inhibited by dexamethasone .

<rna>Human monocyte IL-1 receptor antagonist ( IL-1ra ) messenger ribonucleic acid</rna> ( mRNA ) expression and protein secretion are inhibited by dexamethasone .


We have now further studied the regulation of IL-1ra by the major physiological human glucocorticoid , cortisol .

We have now further studied the regulation of <protein>IL-1ra</protein> by the major physiological human glucocorticoid , cortisol .


We found that cortisol incubation induced a decrease in IL-1ra mRNA expression and a significant inhibition of IL-1ra protein secretion in cell cultures of human peripheral monocytes stimulated with the bacterial endotoxin lipopolysaccharide ( LPS ) .

We found that cortisol incubation induced a decrease in <rna>IL-1ra mRNA</rna> expression and a significant inhibition of <protein>IL-1ra protein</protein> secretion in cell cultures of <cell_type>human peripheral monocytes</cell_type> stimulated with the bacterial endotoxin lipopolysaccharide ( LPS ) .


Oral administration of 276 mumol cortisol to normal subjects also decreased LPS-induced IL-1ra synthesis in cultured monocytes .

Oral administration of 276 mumol cortisol to normal subjects also decreased LPS-induced <protein>IL-1ra</protein> synthesis in <cell_line>cultured monocytes</cell_line> .


By coincubating the monocytes with either the mineralocorticoid antagonist spironolactone or the glucocorticoid receptor antagonist RU 38486 , the in vitro cortisol-induced inhibition of LPS-stimulated IL-1ra secretion was partially reversed .

By coincubating the <cell_type>monocytes</cell_type> with either the mineralocorticoid antagonist spironolactone or the <protein>glucocorticoid receptor</protein> antagonist RU 38486 , the in vitro cortisol-induced inhibition of LPS-stimulated <protein>IL-1ra</protein> secretion was partially reversed .


The mineralocorticoid aldosterone exerted a significant decrease in LPS-induced monocyte IL-1ra secretion in vitro , which was blocked by coincubation with spironolactone .

The mineralocorticoid aldosterone exerted a significant decrease in LPS-induced monocyte <protein>IL-1ra</protein> secretion in vitro , which was blocked by coincubation with spironolactone .


In addition , the expression of mineralocorticoid receptor mRNA in human monocytes was observed by PCR of reversed transcribed RNA .

In addition , the expression of <rna>mineralocorticoid receptor mRNA</rna> in human <cell_type>monocytes</cell_type> was observed by PCR of <rna>reversed transcribed RNA</rna> .


Our results further indicate that corticosteroids physiologically control the IL-1/ IL-1ra system during inflammatory or immune processes .

Our results further indicate that corticosteroids physiologically control the IL-1/ <protein>IL-1ra</protein> system during inflammatory or immune processes .


Moreover , we provide evidence that , in addition to a glucocorticoid receptor -mediated effect , the mineralocorticoid receptor is involved in the inhibition of monocyte IL-1ra secretion by cortisol .

Moreover , we provide evidence that , in addition to a <protein>glucocorticoid receptor</protein> -mediated effect , the <protein>mineralocorticoid receptor</protein> is involved in the inhibition of monocyte <protein>IL-1ra</protein> secretion by cortisol .


Target structures of the CD8 ( + ) -T-cell response to human cytomegalovirus : the 72-kilodalton major immediate-early protein revisited .

Target structures of the CD8 ( + ) -T-cell response to human cytomegalovirus : the <protein>72-kilodalton major immediate-early protein</protein> revisited .


Cell-mediated immunity plays an essential role in the control of infection with the human cytomegalovirus ( HCMV ) .


However , only a few CD8 ( + ) -T-cell epitopes are known , with the majority being contained in the pp65 phosphoprotein , which is believed to dominate the CD8 ( + ) -T-cell response to HCMV .

However , only a few <protein>CD8 ( + ) -T-cell epitopes</protein> are known , with the majority being contained in the <protein>pp65 phosphoprotein</protein> , which is believed to dominate the CD8 ( + ) -T-cell response to HCMV .


Here , we have readdressed the issue of CD8 ( + ) T cells specific for the 72-kDa major immediate-early protein ( IE-1 ) , which is nonstructural but is found very early and throughout the replicative cycle .

Here , we have readdressed the issue of <cell_type>CD8 ( + ) T cells</cell_type> specific for the <protein>72-kDa major immediate-early protein</protein> ( <protein>IE-1</protein> ) , which is nonstructural but is found very early and throughout the replicative cycle .


Using a novel flow-cytometric assay , we were able to identify CD8 ( + ) -T-cell epitopes ( by IE-1 peptide-specific induction of cytokine synthesis ) and simultaneously measure the frequency of cells directed against them .

Using a novel flow-cytometric assay , we were able to identify <protein>CD8 ( + ) -T-cell epitopes</protein> ( by <protein>IE-1</protein> peptide-specific induction of <protein>cytokine</protein> synthesis ) and simultaneously measure the frequency of cells directed against them .


For this purpose , 81 pentadecamer peptides covering the complete 491-amino-acid sequence of IE-1 were tested on peripheral blood mononuclear cells of anti-HCMV immunoglobulin G-seropositive donors .

For this purpose , 81 pentadecamer peptides covering the complete <protein>491-amino-acid sequence</protein> of <protein>IE-1</protein> were tested on <cell_type>peripheral blood mononuclear cells</cell_type> of anti-HCMV immunoglobulin G-seropositive donors .


At least 10 new epitopes were identified , and the fine specificity and presenting HLA molecule of the first of them was determined .

At least 10 new <protein>epitopes</protein> were identified , and the fine specificity and presenting <protein>HLA molecule</protein> of the first of them was determined .


The frequencies of CD8 ( + ) T cells directed against IE-1 were similar to those directed against pp65 in donors tested with known pp65 -derived peptides .

The frequencies of <cell_type>CD8 ( + ) T cells</cell_type> directed against <protein>IE-1</protein> were similar to those directed against <protein>pp65</protein> in donors tested with known <protein>pp65</protein> -derived peptides .


Importantly , additional testing of a corresponding set of peptides covering the complete sequence of pp65 on 10 of these donors identified individuals whose CD8 ( + ) T cells recognized IE-1 but not pp65 and vice versa , clearly illustrating that either protein may be a major target .

Importantly , additional testing of a corresponding set of peptides covering the complete sequence of <protein>pp65</protein> on 10 of these donors identified individuals whose <cell_type>CD8 ( + ) T cells</cell_type> recognized <protein>IE-1</protein> but not <protein>pp65</protein> and vice versa , clearly illustrating that either protein may be a major target .


In summary , our results suggest that IE-1 is far more important as a CD8 ( + ) -T-cell target than current opinion suggests .

In summary , our results suggest that <protein>IE-1</protein> is far more important as a CD8 ( + ) -T-cell target than current opinion suggests .


E1A oncogene induction of cellular susceptibility to killing by cytolytic lymphocytes through target cell sensitization to apoptotic injury .

<dna>E1A oncogene</dna> induction of cellular susceptibility to killing by <cell_type>cytolytic lymphocytes</cell_type> through target cell sensitization to apoptotic injury .


E1A oncogene expression increases mammalian cell susceptibility to lysis by cytolytic lymphocytes ( CLs ) at a stage in this intercellular interaction that is independent of cell surface recognition events .

<dna>E1A oncogene</dna> expression increases mammalian cell susceptibility to lysis by <cell_type>cytolytic lymphocytes</cell_type> ( <cell_type>CLs</cell_type> ) at a stage in this intercellular interaction that is independent of cell surface recognition events .


Since CLs can induce either apoptotic or necrotic cell death , we asked whether E1A sensitization to injury-induced apoptosis is sufficient to explain E1A -induced cytolytic susceptibility .

Since <cell_type>CLs</cell_type> can induce either apoptotic or necrotic cell death , we asked whether <protein>E1A</protein> sensitization to injury-induced apoptosis is sufficient to explain <protein>E1A</protein> -induced cytolytic susceptibility .


Mouse , rat , hamster , and human cells that were rendered cytolytic susceptible by E1A were also sensitized to CL-induced and chemically induced apoptosis .

<cell_type>Mouse , rat , hamster , and human cells</cell_type> that were rendered cytolytic susceptible by <protein>E1A</protein> were also sensitized to CL-induced and chemically induced apoptosis .


In contrast , E1A-positive cells were no more susceptible to injury-induced necrosis than E1A-negative cells .

In contrast , <cell_type>E1A-positive cells</cell_type> were no more susceptible to injury-induced necrosis than <cell_type>E1A-negative cells</cell_type> .


Similar to induction of cytolytic susceptibility and in contrast to other E1A activities , cellular sensitization to chemically induced apoptosis depended on high-level E1A oncoprotein expression .

Similar to induction of cytolytic susceptibility and in contrast to other <protein>E1A</protein> activities , cellular sensitization to chemically induced apoptosis depended on high-level <protein>E1A</protein> <protein>oncoprotein</protein> expression .


Loss of both cytolytic susceptibility and sensitization to chemically induced apoptosis was coselected during in vivo selection of E1A-positive sarcoma cells for increased tumorigenicity .

Loss of both cytolytic susceptibility and sensitization to chemically induced apoptosis was coselected during in vivo selection of <cell_type>E1A-positive sarcoma cells</cell_type> for increased tumorigenicity .


Furthermore , E1A mutant proteins that can not bind the cellular transcriptional coactivator , p300 , and that fail to induce cytolytic susceptibility also failed to sensitize cells to injury-induced apoptosis .

Furthermore , <protein>E1A</protein> <protein>mutant proteins</protein> that can not bind the <protein>cellular transcriptional coactivator</protein> , <protein>p300</protein> , and that fail to induce cytolytic susceptibility also failed to sensitize cells to injury-induced apoptosis .


These data indicate that E1A induces susceptibility to killer cell-induced lysis through sensitization of cells to injury-induced apoptosis .

These data indicate that <protein>E1A</protein> induces susceptibility to killer cell-induced lysis through sensitization of cells to injury-induced apoptosis .


Copyright 1999 Academic Press .


TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues .

<dna>TCL1 oncogene</dna> expression in AIDS-related lymphomas and lymphoid tissues .


AIDS-related non-Hodgkin 's lymphoma ( AIDS NHL ) comprises a diverse and heterogeneous group of high-grade B cell tumors .


Certain classes of AIDS NHL are associated with alterations in oncogenes or tumor-suppressor genes or infections by oncogenic herpesviruses .

Certain classes of AIDS NHL are associated with alterations in <dna>oncogenes</dna> or <dna>tumor-suppressor genes</dna> or infections by oncogenic herpesviruses .


However , the clinically significant class of AIDS NHL designated immunoblastic lymphoma plasmacytoid ( AIDS IBLP ) lacks any consistent genetic alterations .


We identified the TCL1 oncogene from a set of AIDS IBLP-associated cDNA fragments generated by subtractive hybridization with non-AIDS IBLP .

We identified the <dna>TCL1 oncogene</dna> from a set of <dna>AIDS IBLP-associated cDNA fragments</dna> generated by subtractive hybridization with non-AIDS IBLP .


Aberrant TCL1 expression has been implicated in T cell leukemia/lymphoma development , and its expression also has been seen in many established B cell tumor lines .

Aberrant <protein>TCL1</protein> expression has been implicated in T cell leukemia/lymphoma development , and its expression also has been seen in many established <cell_line>B cell tumor lines</cell_line> .


However , TCL1 expression has not been reported in AIDS NHL .

However , <protein>TCL1</protein> expression has not been reported in AIDS NHL .


We find that TCL1 is expressed in the majority of AIDS IBLP tumors examined .

We find that <protein>TCL1</protein> is expressed in the majority of AIDS IBLP tumors examined .


TCL1 protein expression is restricted to tumor cells in AIDS IBLP tissue samples analyzed with immunohistochemical staining .

<protein>TCL1</protein> protein expression is restricted to tumor cells in AIDS IBLP tissue samples analyzed with immunohistochemical staining .


Hyperplastic lymph node and tonsil also exhibit strong TCL1 protein expression in mantle zone B cells and in rare interfollicular zone cells , whereas follicle-center B cells ( centroblasts and centrocytes ) show weaker expression .

Hyperplastic lymph node and tonsil also exhibit strong <protein>TCL1</protein> protein expression in <cell_type>mantle zone B cells</cell_type> and in rare <cell_type>interfollicular zone cells</cell_type> , whereas <cell_type>follicle-center B cells</cell_type> ( <cell_type>centroblasts</cell_type> and <cell_type>centrocytes</cell_type> ) show weaker expression .


These results establish TCL1 as the most prevalent of all of the surveyed oncogenes associated with AIDS IBLP .

These results establish <protein>TCL1</protein> as the most prevalent of all of the surveyed <dna>oncogenes</dna> associated with AIDS IBLP .


They also indicate that abundant TCL1 expression in quiescent mantle zone B cells is down-regulated in activated germinal center follicular B cells in parallel to the known expression pattern of BCL-2 .

They also indicate that abundant <protein>TCL1</protein> expression in <cell_type>quiescent mantle zone B cells</cell_type> is down-regulated in activated <cell_type>germinal center follicular B cells</cell_type> in parallel to the known expression pattern of <protein>BCL-2</protein> .


High-level expression in nonproliferating B cells suggests that TCL1 may function in protecting naive preactivated B cells from apoptosis .

High-level expression in <cell_type>nonproliferating B cells</cell_type> suggests that <protein>TCL1</protein> may function in protecting <cell_type>naive preactivated B cells</cell_type> from apoptosis .


IL-2 -independent activation and proliferation in human T cells induced by CD28 .

<protein>IL-2</protein> -independent activation and proliferation in <cell_type>human T cells</cell_type> induced by <protein>CD28</protein> .


Although the role of CD28 in T cell costimulation is firmly established , the mechanisms by which it exerts its costimulatory actions are less clear .

Although the role of <protein>CD28</protein> in T cell costimulation is firmly established , the mechanisms by which it exerts its costimulatory actions are less clear .


In many circumstances it is difficult to distinguish the effects of CD28 from subsequent actions of cytokines , such as IL-2 , on T cell proliferation .

In many circumstances it is difficult to distinguish the effects of <protein>CD28</protein> from subsequent actions of <protein>cytokines</protein> , such as <protein>IL-2</protein> , on T cell proliferation .


Here , we report a model of CD28 costimulation using PMA plus the natural ligand CD80 that resulted in very limited stimulation of IL-2 , as evidenced by both cytokine production and IL-2 promoter stimulation .

Here , we report a model of <protein>CD28</protein> costimulation using PMA plus the <protein>natural ligand CD80</protein> that resulted in very limited stimulation of <protein>IL-2</protein> , as evidenced by both <protein>cytokine</protein> production and <dna>IL-2 promoter</dna> stimulation .


Promoter assays revealed CD28 -dependent effects on both NF-kappaB and AP-1 , but not on NF-AT or the intact IL-2 promoter .

Promoter assays revealed <protein>CD28</protein> -dependent effects on both <protein>NF-kappaB</protein> and <protein>AP-1</protein> , but not on <protein>NF-AT</protein> or the intact <dna>IL-2 promoter</dna> .


In addition , T cell proliferation was completely resistant to the actions of the immunosuppressant cyclosporin A ( CsA ) .


Moreover T cell proliferation was unaffected by the addition of blocking Abs to both IL-2 and the IL-2 receptor , demonstrating that this form of costimulation by CD28 was independent of IL-2 .

Moreover T cell proliferation was unaffected by the addition of blocking <protein>Abs</protein> to both <protein>IL-2</protein> and the <protein>IL-2 receptor</protein> , demonstrating that this form of costimulation by <protein>CD28</protein> was independent of <protein>IL-2</protein> .


We also investigated the effects of stimulating T cell blasts with CD80 alone and found that there was a limited requirement for IL-2 in this system .

We also investigated the effects of stimulating <cell_type>T cell blasts</cell_type> with <protein>CD80</protein> alone and found that there was a limited requirement for <protein>IL-2</protein> in this system .


We conclude that CD28 costimulation can cause substantial T cell proliferation in the absence of IL-2 , which is driven by a soluble factor independent of NF-AT transactivation .

We conclude that <protein>CD28</protein> costimulation can cause substantial T cell proliferation in the absence of <protein>IL-2</protein> , which is driven by a <protein>soluble factor</protein> independent of <protein>NF-AT</protein> transactivation .


The Epstein-Barr virus latency BamHI-Q promoter is positively regulated by STATs and Zta interference with JAK /STAT activation leads to loss of BamHI-Q promoter activity .

The <dna>Epstein-Barr virus latency BamHI-Q promoter</dna> is positively regulated by <protein>STATs</protein> and <protein>Zta</protein> interference with <protein>JAK</protein> <protein>/STAT</protein> activation leads to loss of <dna>BamHI-Q promoter</dna> activity .


In Epstein-Barr virus ( EBV ) -associated tumors in nonimmunocompromised patients , EBV gene expression is highly restricted .


EBV-encoded nuclear antigen ( EBNA ) -1 is expressed , whereas the immunogenic and proliferative EBNAs are not .

<protein>EBV-encoded nuclear antigen ( EBNA ) -1</protein> is expressed , whereas the immunogenic and proliferative <protein>EBNAs</protein> are not .


This pattern of EBNA expression is generated by usage of the BamHI-Q promoter ( Qp ) .

This pattern of <protein>EBNA</protein> expression is generated by usage of the <dna>BamHI-Q promoter</dna> ( <dna>Qp</dna> ) .


We have determined that the JAK /STAT pathway positively regulates Qp activity .

We have determined that the <protein>JAK</protein> <protein>/STAT</protein> pathway positively regulates <dna>Qp</dna> activity .


In transient-transfection assays , a Qp-CAT reporter was activated by cotransfected JAK-1 and by treatment of cells with the cytokine IL-6 .

In transient-transfection assays , a <dna>Qp-CAT reporter</dna> was activated by cotransfected <protein>JAK-1</protein> and by treatment of cells with the <protein>cytokine</protein> <protein>IL-6</protein> .


The ability of Qp to bind signal transducer and activator of transcription ( STAT ) proteins was directly demonstrated by electrophoretic mobility-shift assay , and mutation of potential STAT-binding sites reduced Qp responsiveness to Janus kinase ( JAK ) -1 .

The ability of <dna>Qp</dna> to bind <protein>signal transducer and activator of transcription ( STAT ) proteins</protein> was directly demonstrated by electrophoretic mobility-shift assay , and mutation of potential <dna>STAT-binding sites</dna> reduced <dna>Qp</dna> responsiveness to <protein>Janus kinase ( JAK ) -1</protein> .


Consistent with a role for STATs in Qp function , Qp using Burkitt 's lymphoma Rael cells and cultured nasopharyngeal carcinoma ( NPC ) cells contained nuclear STAT protein .

Consistent with a role for <protein>STATs</protein> in <dna>Qp</dna> function , <dna>Qp</dna> using <cell_line>Burkitt 's lymphoma Rael cells</cell_line> and <cell_type>cultured nasopharyngeal carcinoma ( NPC ) cells</cell_type> contained nuclear <protein>STAT protein</protein> .


We investigated whether the inability to maintain EBV-positive NPC cell lines in culture was related to Qp activity .

We investigated whether the inability to maintain <cell_line>EBV-positive NPC cell lines</cell_line> in culture was related to <dna>Qp</dna> activity .


Passaging of the NPC cell line HK666 led to activation of expression of BZLF1 , which encodes Zta and loss of Qp function .

Passaging of the <cell_line>NPC cell line HK666</cell_line> led to activation of expression of <dna>BZLF1</dna> , which encodes <protein>Zta</protein> and loss of <dna>Qp</dna> function .


Transient expression assays linked Zta expression to the down-regulation of Qp .

Transient expression assays linked <protein>Zta</protein> expression to the down-regulation of <dna>Qp</dna> .


Cotransfection of Zta reduced Qp activity in reporter assays .

Cotransfection of <protein>Zta</protein> reduced <dna>Qp</dna> activity in reporter assays .


This negative regulation required Zta DNA-binding activity .

This negative regulation required <protein>Zta</protein> DNA-binding activity .


We provide evidence that Zta up-regulation of p53 leads to p53 -mediated interference with JAK /STAT activation of Qp .

We provide evidence that <protein>Zta</protein> up-regulation of <protein>p53</protein> leads to <protein>p53</protein> -mediated interference with <protein>JAK</protein> <protein>/STAT</protein> activation of <dna>Qp</dna> .


The data imply that JAK /STAT signaling has a role in EBV-associated malignancies .

The data imply that <protein>JAK</protein> <protein>/STAT</protein> signaling has a role in EBV-associated malignancies .


Reactive oxygen intermediate-release of fibre-exposed monocytes increases inflammatory cytokine-mRNA level , protein tyrosine kinase and NF-kappaB activity in co-cultured bronchial epithelial cells ( BEAS-2B ) .

Reactive oxygen intermediate-release of <cell_line>fibre-exposed monocytes</cell_line> increases inflammatory <rna>cytokine-mRNA</rna> level , <protein>protein tyrosine kinase</protein> and <protein>NF-kappaB</protein> activity in <cell_line>co-cultured bronchial epithelial cells</cell_line> ( <cell_line>BEAS-2B</cell_line> ) .


Some pulmonary diseases like bronchitis or asthma bronchiale are mediated by inflammatory mechanisms in bronchial epithelial cells .

Some pulmonary diseases like bronchitis or asthma bronchiale are mediated by inflammatory mechanisms in <cell_type>bronchial epithelial cells</cell_type> .


Alveolar macrophages are located directly in the surrounding of these cells , so that we suppose an interaction between epithelial cells and macrophages regarding to the release of inflammatory mediators .

<cell_type>Alveolar macrophages</cell_type> are located directly in the surrounding of these cells , so that we suppose an interaction between <cell_type>epithelial cells</cell_type> and <cell_type>macrophages</cell_type> regarding to the release of <protein>inflammatory mediators</protein> .


For measuring the contribution of macrophages to the release of inflammatory mediators by bronchial epithelial cells , we established an in vitro model of co-cultured blood monocytes ( BM ) and BEAS-2B cells in a transwell system ( Costar ) .

For measuring the contribution of <cell_type>macrophages</cell_type> to the release of <protein>inflammatory mediators</protein> by <cell_type>bronchial epithelial cells</cell_type> , we established an in vitro model of <cell_type>co-cultured blood monocytes</cell_type> ( <cell_type>BM</cell_type> ) and <cell_line>BEAS-2B cells</cell_line> in a transwell system ( Costar ) .


BM were exposed to Chrysotile B and soot particle FR 101 in a concentration of 100 microg/10 ( 6 ) cells .

<cell_type>BM</cell_type> were exposed to Chrysotile B and soot particle FR 101 in a concentration of 100 microg/10 ( 6 ) cells .


After up to 90 min exposure time ELISA , EMSA ( electromobility shift assay ) and RT-PCR were used to measure protein tyrosine kinase activity , protein activity of NF-kappaB and cytokine ( IL-1beta , IL-6 , TNF-alpha ) specific mRNA levels in BEAS-2B cells .

After up to 90 min exposure time ELISA , EMSA ( electromobility shift assay ) and RT-PCR were used to measure <protein>protein tyrosine kinase</protein> activity , protein activity of <protein>NF-kappaB</protein> and <protein>cytokine</protein> ( <protein>IL-1beta</protein> , <protein>IL-6</protein> , <protein>TNF-alpha</protein> ) specific <rna>mRNA</rna> levels in <cell_type>BEAS-2B cells</cell_type> .


We observed an increase in protein tyrosine kinase activity ( up to 1.8 +/- 0.5-fold ) and NF-kappaB protein activity in BEAS-2B cells after particle or fibre exposure of co-cultured BM .

We observed an increase in <protein>protein tyrosine kinase</protein> activity ( up to 1.8 +/- 0.5-fold ) and <protein>NF-kappaB</protein> protein activity in <cell_type>BEAS-2B cells</cell_type> after particle or fibre exposure of <cell_line>co-cultured BM</cell_line> .


Consecutive IL-1beta- , IL-6- and TNF-alpha-mRNA were elevated ( up to 1.9 +/- 0.58-fold ) .

Consecutive <rna>IL-1beta- , IL-6- and TNF-alpha-mRNA</rna> were elevated ( up to 1.9 +/- 0.58-fold ) .


Protein tyrosine kinase activity , NF-kappaB activity , and the synthesis of cytokine-specific mRNA were inhibited by antioxidants .

<protein>Protein tyrosine kinase</protein> activity , <protein>NF-kappaB</protein> activity , and the synthesis of <rna>cytokine-specific mRNA</rna> were inhibited by antioxidants .


These data suggest a ROI-dependent NF-kappaB mediated transcription of inflammatory cytokines in bronchial epithelial cells .

These data suggest a ROI-dependent <protein>NF-kappaB</protein> mediated transcription of <protein>inflammatory cytokines</protein> in <cell_type>bronchial epithelial cells</cell_type> .


Suppression of the human immunodeficiency virus long terminal repeat by CD8+ T cells is dependent on the NFAT-1 element .

Suppression of the <dna>human immunodeficiency virus long terminal repeat</dna> by <cell_type>CD8+ T cells</cell_type> is dependent on the <dna>NFAT-1 element</dna> .


CD8+ T lymphocytes of HIV-1 infected individuals produce a soluble factor that efficiently suppresses HIV-1 replication at the transcriptional level .

<cell_type>CD8+ T lymphocytes</cell_type> of HIV-1 infected individuals produce a <protein>soluble factor</protein> that efficiently suppresses HIV-1 replication at the transcriptional level .


We show here that the response of the HIV-1 long terminal repeat ( LTR ) to mitogenic or Tat -mediated activation is sensitive to the suppressive action of a Herpesvirus saimiri ( HVS ) -transformed CD8+ T cell clone from an HIV-infected individual and supernatants from CD8+ T cells of HIV-1-infected asymptomatic subjects ( CD4+ > 350/microliters ) .

We show here that the response of the HIV-1 long terminal repeat ( <dna>LTR</dna> ) to mitogenic or <protein>Tat</protein> -mediated activation is sensitive to the suppressive action of a <cell_line>Herpesvirus saimiri ( HVS ) -transformed CD8+ T cell clone</cell_line> from an HIV-infected individual and supernatants from <cell_type>CD8+ T cells</cell_type> of HIV-1-infected asymptomatic subjects ( <protein>CD4+</protein> > 350/microliters ) .


Mutagenesis of NF kappa B or Sp-1 elements within the LTR resulted in no change in the ability of CD8+ T cell supernatants to inhibit Tat- or mitogen-mediated LTR transcription .

Mutagenesis of <dna>NF kappa B or Sp-1 elements</dna> within the <dna>LTR</dna> resulted in no change in the ability of <cell_type>CD8+ T cell</cell_type> supernatants to inhibit Tat- or mitogen-mediated LTR transcription .


However , the response to HIV-1 Tat by a LTR in which the interleukin ( IL ) -2 homology NFAT-1 region was mutated resulted in almost complete elimination of suppression by CD8+ T cells .

However , the response to <protein>HIV-1 Tat</protein> by a <dna>LTR</dna> in which the <dna>interleukin ( IL ) -2 homology NFAT-1 region</dna> was mutated resulted in almost complete elimination of suppression by <cell_type>CD8+ T cells</cell_type> .


This was not observed when the NFAT-1 mutant LTR was activated by mitogen .

This was not observed when the <dna>NFAT-1 mutant LTR</dna> was activated by <protein>mitogen</protein> .


We have previously shown that gene expression directed by the HIV-1 NF kappa B elements is inhibited by CD8 + cell-derived supernatants ( Copeland et al. , AIDS Res Hum Retroviruses , 1995 ; 11 : 1321-1326 ) .

We have previously shown that gene expression directed by the HIV-1 <dna>NF kappa B elements</dna> is inhibited by <protein>CD8</protein> + cell-derived supernatants ( Copeland et al. , AIDS Res Hum Retroviruses , 1995 ; 11 : 1321-1326 ) .


Taken together , these observations suggest that mitogenic activation , mediated primarily through the NF kappa B enhancer , is susceptible to CD8 -mediated inhibition , however , inhibition of Tat -mediated activation may rely upon a different pathway that is NFAT-1 dependent .

Taken together , these observations suggest that mitogenic activation , mediated primarily through the <dna>NF kappa B enhancer</dna> , is susceptible to <protein>CD8</protein> -mediated inhibition , however , inhibition of <protein>Tat</protein> -mediated activation may rely upon a different pathway that is <protein>NFAT-1</protein> dependent .


Inhibition of NF-kappa B activation in human T-cell lines by anetholdithiolthione .

Inhibition of <protein>NF-kappa B</protein> activation in <cell_line>human T-cell lines</cell_line> by anetholdithiolthione .


Nuclear factor ( NF ) -kappa B is a redox sensitive cytosolic transcription factor .

<protein>Nuclear factor ( NF ) -kappa B</protein> is a <protein>redox sensitive cytosolic transcription factor</protein> .


Redox regulation of NF-kappa B has been implicated in the activation of the human immuno-deficiency virus ( HIV ) .

Redox regulation of <protein>NF-kappa B</protein> has been implicated in the activation of the human immuno-deficiency virus ( HIV ) .


Therefore , inhibition of NF-kappa B activation may be an effective strategy for acquired immunodeficiency syndrome therapy .

Therefore , inhibition of <protein>NF-kappa B</protein> activation may be an effective strategy for acquired immunodeficiency syndrome therapy .


Anetholdithiolthione ( ADT , 5- [ p-methoxyphenyl ] -3H-1 , 2-dithiol-3-thione ) is an antioxidant which has been used to protect against acetaminophen- and CCl4-induced hepatotoxicity , lipid peroxidation , radiation injury , and also has been used clinically as an anti-choleretic agent .


The present study examined the effect of ADT pretreatment on NF-kappa B activation in response to a variety of stimuli such as H2O2 , phorbol myristate acetate ( PMA ) or tumor necrosis factor alpha ( TNF alpha ) .

The present study examined the effect of ADT pretreatment on <protein>NF-kappa B</protein> activation in response to a variety of stimuli such as H2O2 , phorbol myristate acetate ( PMA ) or <protein>tumor necrosis factor alpha</protein> ( <protein>TNF alpha</protein> ) .


PMA and TNF alpha induced activation of ( NF ) -kappa B in human Jurkat T-cells was partially inhibited by ADT ( 0.1 mM ) pretreatment .

PMA and <protein>TNF alpha</protein> induced activation of <protein>( NF ) -kappa B</protein> in human <cell_line>Jurkat T-cells</cell_line> was partially inhibited by ADT ( 0.1 mM ) pretreatment .


ADT ( 0.1 mM ) also inhibited H2O2 induced activation of the transcription factor in the peroxide sensitive human Wurzburg T-cells .

ADT ( 0.1 mM ) also inhibited H2O2 induced activation of the <protein>transcription factor</protein> in the <cell_line>peroxide sensitive human Wurzburg T-cells</cell_line> .


Furthermore , ADT treated Wurzburg cells had significantly higher glutathione levels as compared with untreated cells .

Furthermore , ADT treated <cell_line>Wurzburg cells</cell_line> had significantly higher glutathione levels as compared with <cell_type>untreated cells</cell_type> .


H2O2 induced lipid peroxidation in Wurzburg cells was remarkably inhibited by ADT pretreatment .

H2O2 induced lipid peroxidation in <cell_line>Wurzburg cells</cell_line> was remarkably inhibited by ADT pretreatment .


ADT , a pro-glutathione antioxidant , was observed to be capable of modulating NF-kappa B activation .

ADT , a pro-glutathione antioxidant , was observed to be capable of modulating <protein>NF-kappa B</protein> activation .


Involvement of tyrosine phosphorylation in endothelial adhesion molecule induction .

Involvement of tyrosine phosphorylation in <protein>endothelial adhesion molecule</protein> induction .


Induction of endothelial adhesion molecules by the cytokine tumor necrosis factor-alpha ( TNF ) can occur independently of protein kinase C and activation of a protein tyrosine kinase ( PTK ) has recently been implicated in the upregulation of vascular cell adhesion molecule 1 ( VCAM-1 ) by interleukin-4 ( IL-4 ) on endothelial cells .

Induction of <protein>endothelial adhesion molecules</protein> by the <protein>cytokine</protein> <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF</protein> ) can occur independently of <protein>protein kinase C</protein> and activation of a <protein>protein tyrosine kinase</protein> ( <protein>PTK</protein> ) has recently been implicated in the upregulation of <protein>vascular cell adhesion molecule 1</protein> ( <protein>VCAM-1</protein> ) by <protein>interleukin-4</protein> ( <protein>IL-4</protein> ) on <cell_type>endothelial cells</cell_type> .


We demonstrate that the PTK inhibitors herbimycin A or genistein suppress induction of endothelial VCAM-1 and E-selectin , as well as subsequent monocytic cell adhesion to endothelial cells stimulated by TNF .

We demonstrate that the <protein>PTK</protein> inhibitors herbimycin A or genistein suppress induction of endothelial <protein>VCAM-1</protein> and <protein>E-selectin</protein> , as well as subsequent monocytic cell adhesion to <cell_type>endothelial cells</cell_type> stimulated by <protein>TNF</protein> .


Inhibition studies indicate that specific tyrosine phosphorylation following PTK activation is involved in the mobilization of the transcription factor , nuclear factor kappa B , and VCAM-1 mRNA expression .

Inhibition studies indicate that specific tyrosine phosphorylation following <protein>PTK</protein> activation is involved in the mobilization of the <protein>transcription factor</protein> , <protein>nuclear factor kappa B</protein> , and <rna>VCAM-1 mRNA</rna> expression .


This may have implications for pathophysiological conditions that involve the upregulation of these molecules ( e.g. inflammation and atherosclerosis ) .


Protein kinase C-zeta mediates NF-kappa B activation in human immunodeficiency virus-infected monocytes .

<protein>Protein kinase C-zeta</protein> mediates <protein>NF-kappa B</protein> activation in <cell_type>human immunodeficiency virus-infected monocytes</cell_type> .


The molecular mechanisms regulating human immunodeficiency virus ( HIV ) persistence in a major cell reservoir such as the macrophage remain unknown .

The molecular mechanisms regulating human immunodeficiency virus ( HIV ) persistence in a major cell reservoir such as the <cell_type>macrophage</cell_type> remain unknown .


NF-kappa B is a transcription factor involved in the regulation of the HIV long terminal repeat and is selectively activated following HIV infection of human macrophages .

<protein>NF-kappa B</protein> is a <protein>transcription factor</protein> involved in the regulation of the <dna>HIV long terminal repeat</dna> and is selectively activated following HIV infection of <cell_type>human macrophages</cell_type> .


Although little information as to what signal transduction pathways mediate NF-kappa B activation in monocytes-macrophages is available , our previous work indicated that classical protein kinase C ( PKC ) isoenzymes were not involved in the HIV-mediated NF-kappa B activation .

Although little information as to what signal transduction pathways mediate <protein>NF-kappa B</protein> activation in <cell_type>monocytes-macrophages</cell_type> is available , our previous work indicated that classical <protein>protein kinase C ( PKC ) isoenzymes</protein> were not involved in the HIV-mediated <protein>NF-kappa B</protein> activation .


In this study , we have focused on atypical PKC isoenzymes .

In this study , we have focused on atypical <protein>PKC isoenzymes</protein> .


PKC-zeta belongs to this family and is known to be an important step in NF-kappa B activation in other cell systems .

<protein>PKC-zeta</protein> belongs to this family and is known to be an important step in <protein>NF-kappa B</protein> activation in other cell systems .


Immunoblotting experiments with U937 cells demonstrate that PKC-zeta is present in these cells , and its expression can be downmodulated by antisense oligonucleotides ( AO ) .

Immunoblotting experiments with <cell_line>U937 cells</cell_line> demonstrate that <protein>PKC-zeta</protein> is present in these cells , and its expression can be downmodulated by antisense oligonucleotides ( AO ) .


The HIV-mediated NF-kappa B activation is selectively reduced by AO to PKC-zeta .

The HIV-mediated <protein>NF-kappa B</protein> activation is selectively reduced by AO to <protein>PKC-zeta</protein> .


In addition , cotransfection of a negative dominant molecule of PKC-zeta ( PKC-zeta mut ) with NF-kappa B -dependent reporter genes selectively inhibits the HIV -but not phorbol myristate acetate- or lipopolysaccharide-mediated activation of NF-kappa B .

In addition , cotransfection of a negative dominant molecule of <protein>PKC-zeta</protein> ( <protein>PKC-zeta mut</protein> ) with <protein>NF-kappa B</protein> -dependent reporter genes selectively inhibits the HIV -but not phorbol myristate acetate- or lipopolysaccharide-mediated activation of <protein>NF-kappa B</protein> .


That PKC-zeta is specific in regulating NF-kappa B is concluded from the inability of PKC-zeta ( mut ) to interfere with the basal or phorbol myristate acetate-inducible CREB -or AP1 -dependent transcriptional activity .

That <protein>PKC-zeta</protein> is specific in regulating <protein>NF-kappa B</protein> is concluded from the inability of <protein>PKC-zeta ( mut )</protein> to interfere with the basal or phorbol myristate acetate-inducible <protein>CREB</protein> -or <protein>AP1</protein> -dependent transcriptional activity .


Lastly , we demonstrate a selective inhibition of p24 production by HIV-infected human macrophages when treated with AO to PKC-zeta .

Lastly , we demonstrate a selective inhibition of <protein>p24</protein> production by <cell_type>HIV-infected human macrophages</cell_type> when treated with AO to <protein>PKC-zeta</protein> .


Altogether , these results suggest that atypical PKC isoenzymes , including PKC-zeta , participate in the signal transduction pathways by which HIV infection results in the activation of NF-kappa B in human monocytic cells and macrophages .

Altogether , these results suggest that <protein>atypical PKC isoenzymes</protein> , including <protein>PKC-zeta</protein> , participate in the signal transduction pathways by which HIV infection results in the activation of <protein>NF-kappa B</protein> in <cell_type>human monocytic cells</cell_type> and <cell_type>macrophages</cell_type> .


Induction of Bcl-x ( L ) expression by human T-cell leukemia virus type 1 Tax through NF-kappaB in apoptosis-resistant T-cell transfectants with Tax .

Induction of <protein>Bcl-x ( L )</protein> expression by <protein>human T-cell leukemia virus type 1 Tax</protein> through <protein>NF-kappaB</protein> in <cell_line>apoptosis-resistant T-cell transfectants</cell_line> with <protein>Tax</protein> .


Human T-cell leukemia virus type 1 ( HTLV-1 ) Tax is thought to play a pivotal role in immortalization of T cells .

Human T-cell leukemia virus type 1 ( HTLV-1 ) <protein>Tax</protein> is thought to play a pivotal role in immortalization of <cell_type>T cells</cell_type> .


We have recently shown that the expression of Tax protected the mouse T-cell line CTLL-2 against apoptosis induced by interleukin-2 ( IL-2 ) deprivation and converted its growth from being IL-2 dependent to being IL-2 independent .

We have recently shown that the expression of <protein>Tax</protein> protected the <cell_line>mouse T-cell line CTLL-2</cell_line> against apoptosis induced by <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) deprivation and converted its growth from being <protein>IL-2</protein> dependent to being <protein>IL-2</protein> independent .


In this study , we demonstrate that constitutive expression of bcl-xl but not bcl-2 , bcl-xs , bak , bad , or bax was associated with apoptosis resistance after IL-2 deprivation in CTLL-2 cells that expressed Tax .

In this study , we demonstrate that constitutive expression of <protein>bcl-xl</protein> but not <protein>bcl-2</protein> , <protein>bcl-xs</protein> , <protein>bak</protein> , <protein>bad</protein> , or <protein>bax</protein> was associated with apoptosis resistance after <protein>IL-2</protein> deprivation in <cell_line>CTLL-2 cells</cell_line> that expressed <protein>Tax</protein> .


Transient-transfection assays showed that bcl-x promoter was transactivated by wild-type Tax .

Transient-transfection assays showed that <dna>bcl-x promoter</dna> was transactivated by <protein>wild-type Tax</protein> .


Similar effects were observed in mutant Tax retaining transactivating ability through NF-kappaB .

Similar effects were observed in mutant <protein>Tax</protein> retaining transactivating ability through <protein>NF-kappaB</protein> .


Deletion or substitution of a putative NF-kappaB binding site identified in the bcl-x promoter significantly decreased Tax -induced transactivation .

Deletion or substitution of a <protein>putative NF-kappaB binding site</protein> identified in the <dna>bcl-x promoter</dna> significantly decreased <protein>Tax</protein> -induced transactivation .


This NF-kappaB-like element was able to form a complex with NF-kappaB family proteins in vitro .

This <dna>NF-kappaB-like element</dna> was able to form a complex with <protein>NF-kappaB family proteins</protein> in vitro .


Furthermore , Tax -induced transactivation of the bcl-x promoter was also diminished by the mutant IkappaBalpha , which specifically inhibits NF-kappaB activity .

Furthermore , <protein>Tax</protein> -induced transactivation of the <dna>bcl-x promoter</dna> was also diminished by the <protein>mutant IkappaBalpha</protein> , which specifically inhibits <protein>NF-kappaB</protein> activity .


Our findings suggest that constitutive expression of Bcl-x ( L ) induced by Tax through the NF-kappaB pathway contributes to the inhibition of apoptosis in CTLL-2 cells after IL-2 deprivation .

Our findings suggest that constitutive expression of <protein>Bcl-x ( L )</protein> induced by <protein>Tax</protein> through the <protein>NF-kappaB</protein> pathway contributes to the inhibition of apoptosis in <cell_line>CTLL-2 cells</cell_line> after <protein>IL-2</protein> deprivation .


The beta-globin promoter is important for recruitment of erythroid Kruppel-like factor to the locus control region in erythroid cells .

The <dna>beta-globin promoter</dna> is important for recruitment of <protein>erythroid Kruppel-like factor</protein> to the <dna>locus control region</dna> in <cell_type>erythroid cells</cell_type> .


Erythroid Kruppel-like factor ( EKLF ) , which binds to the CACCC box in the beta-globin promoter , is required for the expression of the beta-globin gene in adult erythroid cells .

<protein>Erythroid Kruppel-like factor</protein> ( <protein>EKLF</protein> ) , which binds to the CACCC box in the <dna>beta-globin promoter</dna> , is required for the expression of the <dna>beta-globin gene</dna> in <cell_type>adult erythroid cells</cell_type> .


It was recently demonstrated that EKLF is also required for the activity of the beta-globin locus control region ( LCR ) 5'HS3 .

It was recently demonstrated that <protein>EKLF</protein> is also required for the activity of the <dna>beta-globin locus control region</dna> ( <dna>LCR</dna> ) <dna>5'HS3</dna> .


Some evidence suggests that the LCR and the beta-globin promoter interact in adult erythroid cells , and the network of protein-protein interactions that exists between these two elements may regulate how EKLF is recruited to the LCR .

Some evidence suggests that the <dna>LCR</dna> and the <dna>beta-globin promoter</dna> interact in <cell_type>adult erythroid cells</cell_type> , and the network of protein-protein interactions that exists between these two elements may regulate how <protein>EKLF</protein> is recruited to the <dna>LCR</dna> .


In this report , we use the PIN*POINT assay to study the role of the promoter on the recruitment of EKLF to 5'HS2 and 5'HS3 of the LCR .

In this report , we use the PIN*POINT assay to study the role of the promoter on the recruitment of <protein>EKLF</protein> to <dna>5'HS2</dna> and <dna>5'HS3</dna> of the <dna>LCR</dna> .


We find that recruitment of EKLF to 5'HS2 requires the TATA box , but recruitment to 5'HS3 depends on the CACCC and TATA boxes of the beta-globin promoter .

We find that recruitment of <protein>EKLF</protein> to <dna>5'HS2</dna> requires the <dna>TATA box</dna> , but recruitment to <dna>5'HS3</dna> depends on the CACCC and <dna>TATA boxes</dna> of the <dna>beta-globin promoter</dna> .


Furthermore , recruitment of EKLF to 5'HS3 only occurred in beta-globin-expressing murine erythroid leukemia cells , whereas recruitment of EKLF to 5'HS2 occurred in both gamma-globin-expressing K562 cells and murine erythroid leukemia cells .

Furthermore , recruitment of <protein>EKLF</protein> to <dna>5'HS3</dna> only occurred in <cell_type>beta-globin-expressing murine erythroid leukemia cells</cell_type> , whereas recruitment of <protein>EKLF</protein> to <dna>5'HS2</dna> occurred in both <cell_line>gamma-globin-expressing K562 cells</cell_line> and <cell_type>murine erythroid leukemia cells</cell_type> .


Unlike EKLF , Sp1 , which also binds to CACCC boxes , is not recruited to 5'HS3 .

Unlike <protein>EKLF</protein> , <protein>Sp1</protein> , which also binds to CACCC boxes , is not recruited to <dna>5'HS3</dna> .


We have also examined how one 5'HS affects the recruitment of EKLF to another 5'HS .

We have also examined how one <dna>5'HS</dna> affects the recruitment of <protein>EKLF</protein> to another <dna>5'HS</dna> .


We have found that the recruitment of EKLF to 5'HS3 depends on the presence of 5'HS2 in cis , but the recruitment to 5'HS2 does not depend on 5'HS3 .

We have found that the recruitment of <protein>EKLF</protein> to <dna>5'HS3</dna> depends on the presence of <dna>5'HS2</dna> in cis , but the recruitment to <dna>5'HS2</dna> does not depend on <dna>5'HS3</dna> .


Based on these results , we present a model that illustrates how EKLF may be recruited to the beta-globin locus .

Based on these results , we present a model that illustrates how <protein>EKLF</protein> may be recruited to the <dna>beta-globin locus</dna> .


Estrogen decreases TNF gene expression by blocking JNK activity and the resulting production of c-Jun and JunD .

Estrogen decreases <protein>TNF</protein> gene expression by blocking <protein>JNK</protein> activity and the resulting production of <protein>c-Jun</protein> and <protein>JunD</protein> .


Central to the bone-sparing effect of estrogen ( E ( 2 ) ) is its ability to block the monocytic production of the osteoclastogenic cytokine TNF-alpha ( TNF ) .

Central to the bone-sparing effect of estrogen ( E ( 2 ) ) is its ability to block the monocytic production of the <protein>osteoclastogenic cytokine TNF-alpha</protein> ( <protein>TNF</protein> ) .


However , the mechanism by which E ( 2 ) downregulates TNF production is presently unknown .

However , the mechanism by which E ( 2 ) downregulates <protein>TNF</protein> production is presently unknown .


Transient transfection studies in HeLa cells , an E ( 2 ) receptor-negative line , suggest that E ( 2 ) inhibits TNF gene expression through an effect mediated by estrogen receptor beta ( ERbeta ) .

Transient transfection studies in <cell_line>HeLa cells</cell_line> , an E ( 2 ) receptor-negative line , suggest that E ( 2 ) inhibits <protein>TNF</protein> gene expression through an effect mediated by <protein>estrogen receptor beta</protein> ( <protein>ERbeta</protein> ) .


We also report that in RAW 264.7 cells , an E ( 2 ) receptor-positive murine monocytic line , E ( 2 ) downregulates cytokine-induced TNF gene expression by decreasing the activity of the Jun NH ( 2 ) -terminal kinase ( JNK ) .

We also report that in <cell_line>RAW 264.7 cells</cell_line> , an E ( 2 ) receptor-positive murine monocytic line , E ( 2 ) downregulates cytokine-induced <protein>TNF</protein> gene expression by decreasing the activity of the <protein>Jun NH ( 2 ) -terminal kinase</protein> ( <protein>JNK</protein> ) .


The resulting diminished phosphorylation of c-Jun and JunD at their NH ( 2 ) -termini decreases the ability of these nuclear proteins to autostimulate the expression of the c-Jun and JunD genes , thus leading to lower production of c-Jun and JunD .

The resulting diminished phosphorylation of <protein>c-Jun</protein> and <protein>JunD</protein> at their <protein>NH ( 2 ) -termini</protein> decreases the ability of these nuclear proteins to autostimulate the expression of the <dna>c-Jun and JunD genes</dna> , thus leading to lower production of <protein>c-Jun</protein> and <protein>JunD</protein> .


The consequent decrease in the nuclear levels of c-Jun and JunD leads to diminished binding of c-Jun/c-Fos and JunD/c-Fos heterodimers to the AP-1 consensus sequence in the TNF promoter and , thus , to decreased transactivation of the TNF gene .

The consequent decrease in the nuclear levels of <protein>c-Jun</protein> and <protein>JunD</protein> leads to diminished binding of <protein>c-Jun/c-Fos</protein> and <protein>JunD/c-Fos heterodimers</protein> to the <dna>AP-1 consensus sequence</dna> in the <dna>TNF promoter</dna> and , thus , to decreased transactivation of the <dna>TNF gene</dna> .


Cutting edge : TCR stimulation by antibody and bacterial superantigen induces Stat3 activation in human T cells .

Cutting edge : <protein>TCR</protein> stimulation by antibody and bacterial superantigen induces <protein>Stat3</protein> activation in <cell_type>human T cells</cell_type> .


Recent data show that TCR/CD3 stimulation induces activation of Stat5 in murine T cells .

Recent data show that <protein>TCR/CD3</protein> stimulation induces activation of <protein>Stat5</protein> in <cell_type>murine T cells</cell_type> .


Here , we show that CD3 ligation by mAb and Staphylococcal enterotoxin ( SE ) induce a rapid , gradually accumulating , long-lasting tyrosine , and serine phosphorylation of Stat3 ( but not Stat5 ) in allogen-specific human CD4+ T cell lines .

Here , we show that CD3 ligation by mAb and Staphylococcal enterotoxin ( SE ) induce a rapid , gradually accumulating , long-lasting tyrosine , and serine phosphorylation of <protein>Stat3</protein> ( but not <protein>Stat5</protein> ) in <cell_line>allogen-specific human CD4+ T cell lines</cell_line> .


In contrast , IL-2 induces a rapid and transient tyrosine and serine phosphorylation of Stat3 .

In contrast , <protein>IL-2</protein> induces a rapid and transient tyrosine and serine phosphorylation of <protein>Stat3</protein> .


Compared with IL-2 , CD3 ligation induces a delayed Stat3 binding to oligonucleotide probes from the ICAM-1 and IL-2R alpha promoter .

Compared with <protein>IL-2</protein> , <protein>CD3</protein> ligation induces a delayed <protein>Stat3</protein> binding to oligonucleotide probes from the <protein>ICAM-1</protein> and <dna>IL-2R alpha promoter</dna> .


CD3 -mediated activation of Stat3 is almost completely inhibited by a Src kinase inhibitor ( PP1 ) , whereas IL-2 -induced Stat3 activation is unaffected .

<protein>CD3</protein> -mediated activation of <protein>Stat3</protein> is almost completely inhibited by a <protein>Src kinase inhibitor</protein> ( <protein>PP1</protein> ) , whereas <protein>IL-2</protein> -induced <protein>Stat3</protein> activation is unaffected .


In conclusion , we show that CD3 ligation by mAb and SE triggers a rapid , PP1 -sensitive tyrosine and serine phosphorylation of Stat3 in human CD4+ T cells .

In conclusion , we show that <protein>CD3</protein> ligation by <protein>mAb</protein> and SE triggers a rapid , <protein>PP1</protein> -sensitive tyrosine and serine phosphorylation of <protein>Stat3</protein> in <cell_type>human CD4+ T cells</cell_type> .


Moreover , we provide evidence that TCR/CD3 and IL-2 induce Stat3 activation via distinct signaling pathways .

Moreover , we provide evidence that <protein>TCR/CD3</protein> and <protein>IL-2</protein> induce <protein>Stat3</protein> activation via distinct signaling pathways .


Distinctive gene expression patterns in human mammary epithelial cells and breast cancers .

Distinctive gene expression patterns in <cell_type>human mammary epithelial cells</cell_type> and breast cancers .


cDNA microarrays and a clustering algorithm were used to identify patterns of gene expression in human mammary epithelial cells growing in culture and in primary human breast tumors .

<dna>cDNA microarrays</dna> and a clustering algorithm were used to identify patterns of gene expression in <cell_type>human mammary epithelial cells</cell_type> growing in culture and in primary human breast tumors .


Clusters of coexpressed genes identified through manipulations of mammary epithelial cells in vitro also showed consistent patterns of variation in expression among breast tumor samples .

Clusters of <dna>coexpressed genes</dna> identified through manipulations of <cell_type>mammary epithelial cells</cell_type> in vitro also showed consistent patterns of variation in expression among breast tumor samples .


By using immunohistochemistry with antibodies against proteins encoded by a particular gene in a cluster , the identity of the cell type within the tumor specimen that contributed the observed gene expression pattern could be determined .


Clusters of genes with coherent expression patterns in cultured cells and in the breast tumors samples could be related to specific features of biological variation among the samples .

Clusters of <dna>genes</dna> with coherent expression patterns in <cell_type>cultured cells</cell_type> and in the breast tumors samples could be related to specific features of biological variation among the samples .


Two such clusters were found to have patterns that correlated with variation in cell proliferation rates and with activation of the IFN -regulated signal transduction pathway , respectively .

Two such clusters were found to have patterns that correlated with variation in cell proliferation rates and with activation of the <protein>IFN</protein> -regulated signal transduction pathway , respectively .


Clusters of genes expressed by stromal cells and lymphocytes in the breast tumors also were identified in this analysis .

Clusters of <dna>genes</dna> expressed by <cell_type>stromal cells</cell_type> and <cell_type>lymphocytes</cell_type> in the breast tumors also were identified in this analysis .


These results support the feasibility and usefulness of this systematic approach to studying variation in gene expression patterns in human cancers as a means to dissect and classify solid tumors .


PPARgamma activation induces the expression of the adipocyte fatty acid binding protein gene in human monocytes .

<protein>PPARgamma</protein> activation induces the expression of the <dna>adipocyte fatty acid binding protein gene</dna> in <cell_type>human monocytes</cell_type> .


The peroxisome-proliferator activated receptor gamma ( PPARgamma ) , a member of the nuclear receptor superfamily of ligand activated transcription factors , plays a key role in the anti-diabetic actions of the thiazolidinediones ( TZDs ) .

The <protein>peroxisome-proliferator activated receptor gamma</protein> ( <protein>PPARgamma</protein> ) , a member of the <protein>nuclear receptor superfamily</protein> of <protein>ligand activated transcription factors</protein> , plays a key role in the anti-diabetic actions of the thiazolidinediones ( TZDs ) .


PPARgamma induces the expression of many genes involved in lipid anabolism , including the adipocyte fatty acid binding protein ( aP2 ) , and is a key regulator of adipocyte differentiation .

<protein>PPARgamma</protein> induces the expression of many <dna>genes</dna> involved in lipid anabolism , including the <protein>adipocyte fatty acid binding protein</protein> ( <protein>aP2</protein> ) , and is a key regulator of <cell_type>adipocyte</cell_type> differentiation .


PPARgamma is also expressed in hematopoietic cells and is up-regulated in activated monocytes/macrophages .

<protein>PPARgamma</protein> is also expressed in <cell_type>hematopoietic cells</cell_type> and is up-regulated in activated <cell_type>monocytes/macrophages</cell_type> .


Activation of PPARgamma may play a role in the induction of differentiation of macrophages to foam cells that are associated with atherosclerotic lesions .

Activation of <protein>PPARgamma</protein> may play a role in the induction of differentiation of <cell_type>macrophages</cell_type> to <cell_type>foam cells</cell_type> that are associated with atherosclerotic lesions .


We report that both natural and synthetic PPARgamma agonists induce time- and dose-dependent increases in aP2 mRNA in both primary human monocytes and the monocytic cell line , THP-1 .

We report that both natural and synthetic PPARgamma agonists induce time- and dose-dependent increases in <rna>aP2 mRNA</rna> in both <cell_type>primary human monocytes</cell_type> and the <cell_line>monocytic cell line</cell_line> , <cell_line>THP-1</cell_line> .


These data suggest that PPARgamma activation may play a role in monocyte differentiation and function analogous to its well-characterized role in adipocytes .

These data suggest that <protein>PPARgamma</protein> activation may play a role in <cell_type>monocyte</cell_type> differentiation and function analogous to its well-characterized role in <cell_type>adipocytes .</cell_type>


Identification of a physical interaction between calcineurin and nuclear factor of activated T cells ( NFATp ) .

Identification of a physical interaction between <protein>calcineurin</protein> and <protein>nuclear factor of activated T cells</protein> ( <protein>NFATp</protein> ) .


In T lymphocytes , the calcium/calmodulin-dependent serine/threonine phosphatase , calcineurin , plays a pivotal role in transducing membrane-associated signals to the nucleus .

In <cell_type>T lymphocytes</cell_type> , the <protein>calcium/calmodulin-dependent serine/threonine phosphatase</protein> , <protein>calcineurin</protein> , plays a pivotal role in transducing membrane-associated signals to the nucleus .


One of the putative targets of calcineurin is the pre-existing , cytosolic component of the nuclear factor of activated T cells ( NFATp ; also referred to as NFAT1 ) , which is one of several transcription factors required for the expression of interleukin 2 .

One of the putative targets of <protein>calcineurin</protein> is the pre-existing , <protein>cytosolic component</protein> of the <protein>nuclear factor of activated T cells</protein> ( <protein>NFATp</protein> ; also referred to as <protein>NFAT1</protein> ) , which is one of several <protein>transcription factors</protein> required for the expression of <protein>interleukin 2</protein> .


Inhibition of calcineurin by the immunosuppressive drugs cyclosporin A and FK506 prevents dephosphorylation of NFATp and its translocation to the nucleus .

Inhibition of <protein>calcineurin</protein> by the immunosuppressive drugs cyclosporin A and FK506 prevents dephosphorylation of <protein>NFATp</protein> and its translocation to the nucleus .


However , a physical interaction between calcineurin and NFATp has not been demonstrated .

However , a physical interaction between <protein>calcineurin</protein> and <protein>NFATp</protein> has not been demonstrated .


Here we demonstrate the binding of NFATp from lysates of T cells to immobilized calcineurin .

Here we demonstrate the binding of <protein>NFATp</protein> from lysates of <cell_type>T cells</cell_type> to immobilized <protein>calcineurin</protein> .


Stimulation of T cells with calcium ionophore induced a shift in the molecular weight of NFATp that is due to its dephosphorylation .

Stimulation of <cell_type>T cells</cell_type> with calcium ionophore induced a shift in the molecular weight of <protein>NFATp</protein> that is due to its dephosphorylation .


This dephosphorylation was inhibited by treatment of T cells with cyclosporin A or FK506 prior to stimulation .

This dephosphorylation was inhibited by treatment of <cell_type>T cells</cell_type> with cyclosporin A or FK506 prior to stimulation .


Of note , both the phosphorylated and the dephosphorylated form of NFATp bound to calcineurin .

Of note , both the phosphorylated and the dephosphorylated form of <protein>NFATp</protein> bound to <protein>calcineurin</protein> .


Furthermore , the binding of both forms of NFATp to calcineurin was inhibited by pretreatment of calcineurin with a complex of FK506 and its ligand FKBP12 .

Furthermore , the binding of both forms of <protein>NFATp</protein> to <protein>calcineurin</protein> was inhibited by pretreatment of <protein>calcineurin</protein> with a complex of FK506 and its ligand FKBP12 .


Taken together these data strongly suggest a direct interaction of calcineurin with NFATp and that this interaction does not depend upon the phosphorylation sites of NFATp affected by activation .

Taken together these data strongly suggest a direct interaction of <protein>calcineurin</protein> with <protein>NFATp</protein> and that this interaction does not depend upon the <dna>phosphorylation sites</dna> of <protein>NFATp</protein> affected by activation .


Cross-linking CD40 on B cells preferentially induces stress-activated protein kinases rather than mitogen-activated protein kinases .

Cross-linking <protein>CD40</protein> on <cell_type>B cells</cell_type> preferentially induces <protein>stress-activated protein kinases</protein> rather than <protein>mitogen-activated protein kinases</protein> .


The B cell-associated surface molecule CD40 plays a key role in T cell-dependent B cell maturation , as individuals with defects in either CD40 or its ligand are impaired in immunoglobulin isotype class switching and germinal center formation .

The <protein>B cell-associated surface molecule</protein> <protein>CD40</protein> plays a key role in T cell-dependent B cell maturation , as individuals with defects in either <protein>CD40</protein> or its ligand are impaired in <protein>immunoglobulin</protein> isotype class switching and germinal center formation .


CD40 signaling activates downstream effectors , including the tyrosine protein kinase , Lyn , the phosphatidylinositol-3-kinase ( PI-3 kinase ) , and the transcription factor , NF-kappa B .

<protein>CD40</protein> signaling activates <protein>downstream effectors</protein> , including the <protein>tyrosine protein kinase</protein> , <protein>Lyn</protein> , the <protein>phosphatidylinositol-3-kinase</protein> ( <protein>PI-3 kinase</protein> ) , and the transcription factor , <protein>NF-kappa B</protein> .


In this study , we demonstrate that stress-activated protein kinases ( SAPK ) are activated after CD40 cross-linking on various B cell lines or human tonsillar B cells .

In this study , we demonstrate that <protein>stress-activated protein kinases</protein> ( <protein>SAPK</protein> ) are activated after <protein>CD40</protein> cross-linking on various <cell_line>B cell lines</cell_line> or <cell_type>human tonsillar B cells</cell_type> .


The activation is rapid and transient and is mediated through a cyclosporin A-insensitive pathway .


Furthermore , this signaling pathway appears not to rely on protein kinase C .

Furthermore , this signaling pathway appears not to rely on <protein>protein kinase C</protein> .


While CD40 ligation strongly activates the SAPKs ( up to 25-fold ) , it does not affect members of the mitogen-activated protein kinase family ( MAPK ; ERK1 and ERK2 ) .

While <protein>CD40</protein> ligation strongly activates the <protein>SAPKs</protein> ( up to 25-fold ) , it does not affect members of the <protein>mitogen-activated protein kinase family</protein> ( <protein>MAPK</protein> ; <protein>ERK1</protein> and <protein>ERK2</protein> ) .


Consistent with these data , CD40 signals up-regulate c-jun but not c-fos mRNA and alter the transcription factor ATF2 but not the Raf-1 protein .

Consistent with these data , <protein>CD40</protein> signals up-regulate <rna>c-jun but not c-fos mRNA</rna> and alter the <protein>transcription factor</protein> <protein>ATF2</protein> but not the <protein>Raf-1 protein</protein> .


In summary , CD40 signaling preferentially induces SAPK but not MAPK .

In summary , <protein>CD40</protein> signaling preferentially induces <protein>SAPK</protein> but not <protein>MAPK</protein> .


Stimulation of the T-cell antigen receptor-CD3 complex signaling pathway by the tyrosine phosphatase inhibitor pervanadate is mediated by inhibition of CD45 : evidence for two interconnected Lck/Fyn- or zap-70-dependent signaling pathways .

Stimulation of the <protein>T-cell antigen receptor-CD3 complex</protein> signaling pathway by the <protein>tyrosine phosphatase</protein> inhibitor pervanadate is mediated by inhibition of <protein>CD45</protein> : evidence for two interconnected Lck/Fyn- or zap-70-dependent signaling pathways .


The tyrosine phosphatase specific inhibitor pervanadate is a potent activator of T lymphocytes through induction of tyrosine phosphorylation and downstream events of the activation cascade .

The <protein>tyrosine phosphatase</protein> specific inhibitor pervanadate is a potent activator of <cell_type>T lymphocytes</cell_type> through induction of <protein>tyrosine phosphorylation</protein> and downstream events of the activation cascade .


Using CD45- or CD3-negative variants of the Jurkat leukemic T-cell line we show that the different biochemical events induced by pervanadate appeared to be dependent on the presence at the cell surface of either CD45 or CD3 .

Using <cell_line>CD45- or CD3-negative variants</cell_line> of the <cell_line>Jurkat leukemic T-cell line</cell_line> we show that the different biochemical events induced by pervanadate appeared to be dependent on the presence at the cell surface of either <protein>CD45</protein> or <protein>CD3</protein> .


CD45 -dependent events such as tyrosine phosphorylation of Shc , activation of nuclear factor-kappa B ( NF-kappa B ) , activator protein-1 ( AP-1 ) , transcription factors , and stimulation of interleukin-2 ( IL-2 ) promoter and of CD69 and CD25 surface expression paralleled activation of the tyrosine kinases lck and fyn .

<protein>CD45</protein> -dependent events such as <protein>tyrosine phosphorylation</protein> of <protein>Shc</protein> , activation of <protein>nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) , <protein>activator protein-1</protein> ( <protein>AP-1</protein> ) , <protein>transcription factors</protein> , and stimulation of <dna>interleukin-2 ( IL-2 ) promoter</dna> and of <protein>CD69</protein> and <protein>CD25</protein> surface expression paralleled activation of the <protein>tyrosine kinases</protein> <protein>lck</protein> and <protein>fyn</protein> .


By contrast , stimulation of calcium influx , a CD3 -dependent event , paralleled zap-70 activation .

By contrast , stimulation of calcium influx , a <protein>CD3</protein> -dependent event , paralleled <protein>zap-70</protein> activation .


The data demonstrate that the T-cell antigen receptor -CD3 ( TcR-CD3 ) complex is functionally linked to two different protein tyrosine kinase ( PTK ) modules with separate specific functions and that CD45 may be an important regulator of this coupling .

The data demonstrate that the T-cell antigen receptor <protein>-CD3 ( TcR-CD3 ) complex</protein> is functionally linked to two different <protein>protein tyrosine kinase</protein> ( <protein>PTK</protein> ) modules with separate specific functions and that <protein>CD45</protein> may be an important regulator of this coupling .


Vitamin D analogs , 20-Epi-22-oxa-24a , 26a , 27a , -trihomo-1alpha , 25 ( OH ) 2-vitamin D3 , 1 , 24 ( OH ) 2-22-ene-24-cyclopropyl-vitamin D3 and 1alpha , 25 ( OH ) 2-lumisterol3 prime NB4 leukemia cells for monocytic differentiation via nongenomic signaling pathways , involving calcium and calpain .

Vitamin D analogs , 20-Epi-22-oxa-24a , 26a , 27a , -trihomo-1alpha , 25 ( OH ) 2-vitamin D3 , 1 , 24 ( OH ) 2-22-ene-24-cyclopropyl-vitamin D3 and 1alpha , 25 ( OH ) 2-lumisterol3 prime <cell_line>NB4 leukemia cells</cell_line> for monocytic differentiation via nongenomic signaling pathways , involving calcium and calpain .


Side-chain modified vitamin D analogs including 20-Epi-22-oxa-24a , 26a , 27a-trihomo-1alpha , 2 5-dihydroxyvitamin D3 ( KH1060 ) , and 1 , 24-dihydroxy-22-ene-24-cyclopropyl-vitamin D3 ( MC903 ) were originally designed to aid in the treatment of hyperproliferative disorders including psoriasis and cancer .


Here we demonstrate that these analogs , as well as the 6-cis-locked conformer , 1alpha , 25-dihydroxy-lumisterol3 ( JN ) prime NB4 cells for monocytic differentiation .

Here we demonstrate that these analogs , as well as the 6-cis-locked conformer , <cell_line>1alpha , 25-dihydroxy-lumisterol3 ( JN ) prime NB4 cells</cell_line> for monocytic differentiation .


Previously , the action of MC903 and KH1060 was presumed to be mediated by the nuclear vitamin D receptor ( VDRnuc ) .

Previously , the action of MC903 and KH1060 was presumed to be mediated by the <protein>nuclear vitamin D receptor</protein> ( <protein>VDRnuc</protein> ) .


Differentiation in response to all analogs was shown to be inhibited by 1beta , 25-dihydroxyvitamin D3 ( HL ) , the antagonist to the nongenomic activities of 1 , 25D3 .


These data suggest that although MC903 and KH1060 may bind the VDRnuc , that the differentiative activities of these agents requires nongenomic signaling pathways .

These data suggest that although MC903 and KH1060 may bind the <protein>VDRnuc</protein> , that the differentiative activities of these agents requires nongenomic signaling pathways .


Here we show that 1alpha , 25 ( OH ) 2-d5-previtamin D3 ( HF ) , JN , KH1060 , and MC903 induce expression of PKC alpha and PKC delta and translocation of both isoforms to the particulate fraction , and PKC alpha to the nuclear fraction .

Here we show that 1alpha , 25 ( OH ) 2-d5-previtamin D3 ( HF ) , JN , KH1060 , and MC903 induce expression of <protein>PKC alpha</protein> and <protein>PKC delta</protein> and translocation of both isoforms to the particulate fraction , and <protein>PKC alpha</protein> to the nuclear fraction .


The full differentiation response with combinations of analogs and TPA was inhibited 50 % by the membrane permeable Ca2+ chelator , 1 , 2-bis ( o-aminophenoxy ) -ethane-N , N , N ' , N'-tetraacetic acid ( BAPTA-AM ) or calpain inhibitor I .

The full differentiation response with combinations of analogs and TPA was inhibited 50 % by the membrane permeable Ca2+ chelator , 1 , 2-bis ( o-aminophenoxy ) -ethane-N , N , N ' , N'-tetraacetic acid ( BAPTA-AM ) or <protein>calpain</protein> inhibitor I .


These data demonstrate that intracellular free calcium and the calcium-dependent protease , calpain play critical roles in monocytic differentiation .

These data demonstrate that intracellular free calcium and the <protein>calcium-dependent protease</protein> , <protein>calpain</protein> play critical roles in monocytic differentiation .


Intracellular calcium appears to be most critical in the 1 , 25D3-priming stage of differentiation , while calpain is essential in the TPA maturation response .

Intracellular calcium appears to be most critical in the 1 , 25D3-priming stage of differentiation , while <protein>calpain</protein> is essential in the TPA maturation response .


Neutrophil maturation and the role of retinoic acid .

<cell_type>Neutrophil</cell_type> maturation and the role of retinoic acid .


Neutrophil maturation occurs in well defined morphological stages that correlate with the acquisition of molecular markers associated with neutrophil function .

<cell_type>Neutrophil</cell_type> maturation occurs in well defined morphological stages that correlate with the acquisition of <protein>molecular markers</protein> associated with neutrophil function .


A variety of factors are known to play a role in terminal neutrophil maturation , including the vitamin A derivative , retinoic acid .

A variety of factors are known to play a role in terminal <cell_type>neutrophil</cell_type> maturation , including the vitamin A derivative , retinoic acid .


Retinoic acid can directly modulate gene expression via binding to its nuclear receptors , which can , in turn , activate transcription of target genes .

Retinoic acid can directly modulate gene expression via binding to its <protein>nuclear receptors</protein> , which can , in turn , activate transcription of <dna>target genes</dna> .


A role for retinoic acid during neutrophil maturation has been suggested from a variety of sources. Here we present a review of the mechanism of retinoic acid receptor action and the major evidence showing that normal retinoid signaling is required for neutrophil maturation .

A role for retinoic acid during <cell_type>neutrophil</cell_type> maturation has been suggested from a variety of sources. Here we present a review of the mechanism of <protein>retinoic acid receptor</protein> action and the major evidence showing that normal retinoid signaling is required for <cell_type>neutrophil</cell_type> maturation .


Human T-cell lymphotrophic virus type-I tax gene induces secretion of human macrophage inflammatory protein-1alpha .

<dna>Human T-cell lymphotrophic virus type-I tax gene</dna> induces secretion of <protein>human macrophage inflammatory protein-1alpha</protein> .


Human T-cell lymphotropic virus I ( HTLV-I ) encodes for a 40-kDa protein , Tax , which is important for the immortalization of T cells .

Human T-cell lymphotropic virus I ( HTLV-I ) encodes for a <protein>40-kDa protein</protein> , <protein>Tax</protein> , which is important for the immortalization of <cell_type>T cells</cell_type> .


Tax has been shown to transactivate several cellular genes .

<protein>Tax</protein> has been shown to transactivate several <dna>cellular genes</dna> .


In this study , we show that MIP-1alpha is selectively expressed and secreted in the tax transfected Jurkat cell line upon mitogen stimulation .

In this study , we show that <protein>MIP-1alpha</protein> is selectively expressed and secreted in the <cell_line>tax transfected Jurkat cell line</cell_line> upon <protein>mitogen</protein> stimulation .


Expression of MIP-1alpha-R mRNA in these cells suggests an autocrine role for this chemokine in HTLV-I infected T-cells .

Expression of <rna>MIP-1alpha-R mRNA</rna> in these cells suggests an autocrine role for this <protein>chemokine</protein> in <cell_type>HTLV-I infected T-cells</cell_type> .


Induced MIP-1alpha expression and secretion in PMA/PHA stimulated tax transfected cells correlate with the noninduction of MNP-1 transcription factor , which is intimately involved in downmodulating the MIP-1alpha gene .

Induced <protein>MIP-1alpha</protein> expression and secretion in <cell_line>PMA/PHA stimulated tax transfected cells</cell_line> correlate with the noninduction of <protein>MNP-1</protein> <protein>transcription factor</protein> , which is intimately involved in downmodulating the <dna>MIP-1alpha gene</dna> .


Copyright 1999 Academic Press .


Dendritic cells and the pathogenesis of rheumatoid arthritis .

<cell_type>Dendritic cells</cell_type> and the pathogenesis of rheumatoid arthritis .


Rheumatoid arthritis ( RA ) is a chronic autoimmune inflammatory disease in which unknown arthrogenic autoantigen is presented to CD4+ T cells .

Rheumatoid arthritis ( RA ) is a chronic autoimmune inflammatory disease in which unknown <protein>arthrogenic autoantigen</protein> is presented to <cell_type>CD4+ T cells</cell_type> .


The strong association of the disease with an epitope within the HLA-DR chain shared between various alleles of HLA-DR4 and DR1 emphasizes the importance of antigen presentation .

The strong association of the disease with an <protein>epitope</protein> within the <protein>HLA-DR chain</protein> shared between various alleles of <protein>HLA-DR4</protein> and <protein>DR1</protein> emphasizes the importance of antigen presentation .


This immune response predominantly occurs in the synovial tissue and fluid of the joints and autoreactive T cells are readily demonstrable in both the synovial compartment and blood .

This immune response predominantly occurs in the synovial tissue and fluid of the joints and <cell_type>autoreactive T cells</cell_type> are readily demonstrable in both the synovial compartment and blood .


Circulating dendritic cells ( DC ) are phenotypically and functionally identical with normal peripheral blood ( PB ) DC .

<cell_type>Circulating dendritic cells</cell_type> ( <cell_type>DC</cell_type> ) are phenotypically and functionally identical with <cell_type>normal peripheral blood ( PB ) DC</cell_type> .


In the synovial tissue , fully differentiated perivascular DC are found in close association with T cells and with B cell follicles , sometimes containing follicular DC .

In the synovial tissue , fully differentiated <cell_type>perivascular DC</cell_type> are found in close association with <cell_type>T cells</cell_type> and with <cell_type>B cell follicles</cell_type> , sometimes containing <cell_type>follicular DC</cell_type> .


These perivascular DC migrate across the activated endothelium from blood and receive differentiative signals within the joint from monocyte-derived cytokines and CD40-ligand+ T cells .

These <cell_type>perivascular DC</cell_type> migrate across the activated endothelium from blood and receive differentiative signals within the joint from <protein>monocyte-derived cytokines</protein> and <cell_type>CD40-ligand+ T cells</cell_type> .


In the SF , DC manifest an intermediate phenotype , similar to that of monocyte-derived DC in vitro .

In the SF , <cell_type>DC</cell_type> manifest an intermediate phenotype , similar to that of <cell_type>monocyte-derived DC</cell_type> in vitro .


Like a delayed-type hypersensitivity response , the rheumatoid synovium represents an effector site .


DC at many effector sites have a characteristic pattern of infiltration and differentiation .


It is important to note that the effector response is not self-limiting in RA autoimmune inflammation .


In this article , we argue that the presentation of self-antigen by DC and by autoantibody-producing B cells is critical for the perpetuation of the autoimmune response .

In this article , we argue that the presentation of <protein>self-antigen</protein> by <cell_type>DC</cell_type> and by <cell_type>autoantibody-producing B cells</cell_type> is critical for the perpetuation of the autoimmune response .


Permanently arresting this ongoing immune response with either pharmaceutical agents or immunotherapy is a major challenge for immunology .


Thymocyte-thymic epithelial cell interaction leads to high-level replication of human immunodeficiency virus exclusively in mature CD4 ( + ) CD8 ( - ) CD3 ( + ) thymocytes : a critical role for tumor necrosis factor and interleukin-7 .

Thymocyte-thymic <cell_type>epithelial cell</cell_type> interaction leads to high-level replication of human immunodeficiency virus exclusively in <cell_type>mature CD4 ( + ) CD8 ( - ) CD3 ( + ) thymocytes</cell_type> : a critical role for <protein>tumor necrosis factor</protein> and <protein>interleukin-7</protein> .


This work aims at identifying the thymocyte subpopulation able to support human immunodeficiency virus ( HIV ) replication under the biological stimuli of the thymic microenvironment .


In this report we demonstrate that interaction with thymic epithelial cells ( TEC ) induces a high-level replication of the T-tropic primary isolate HIV-1 ( B-LAIp ) exclusively in the mature CD4 ( + ) CD8 ( - ) CD3 ( + ) thymocytes .

In this report we demonstrate that interaction with <cell_type>thymic epithelial cells</cell_type> ( <cell_type>TEC</cell_type> ) induces a high-level replication of the <protein>T-tropic primary isolate HIV-1</protein> ( <protein>B-LAIp</protein> ) exclusively in the mature <cell_type>CD4 ( + ) CD8 ( - ) CD3 ( + ) thymocytes</cell_type> .


Tumor necrosis factor ( TNF ) and interleukin-7 ( IL-7 ) , secreted during this interaction , are critical cytokines for HIV long terminal repeat transactivation through NF-kappaB -dependent activation .

<protein>Tumor necrosis factor</protein> ( <protein>TNF</protein> ) and <protein>interleukin-7</protein> ( <protein>IL-7</protein> ) , secreted during this interaction , are critical cytokines for <dna>HIV long terminal repeat</dna> transactivation through <protein>NF-kappaB</protein> -dependent activation .


TNF is the major inducer of NF-kappaB and particularly of the p50-p65 complex , whereas IL-7 acts as a cofactor by sustaining the expression of the p75 TNF receptor .

<protein>TNF</protein> is the major inducer of <protein>NF-kappaB</protein> and particularly of the <protein>p50-p65 complex</protein> , whereas <protein>IL-7</protein> acts as a cofactor by sustaining the expression of the <protein>p75 TNF receptor</protein> .


The requirement for TNF is further confirmed by the observation that the inability of the intermediate CD4 ( + ) CD8 ( - ) CD3 ( - ) thymocytes to replicate the virus is associated with a defect in TNF production during their interaction with TEC and correlates with the absence of nuclear NF-kappaB activity in these freshly isolated thymocytes .

The requirement for <protein>TNF</protein> is further confirmed by the observation that the inability of the <cell_type>intermediate CD4 ( + ) CD8 ( - ) CD3 ( - ) thymocytes</cell_type> to replicate the virus is associated with a defect in <protein>TNF</protein> production during their interaction with <cell_type>TEC</cell_type> and correlates with the absence of nuclear <protein>NF-kappaB</protein> activity in these <cell_type>freshly isolated thymocytes</cell_type> .


Addition of exogenous TNF to the intermediate thymocyte cultures induces NF-kappaB activity and is sufficient to promote HIV replication in the cocultures with TEC .

Addition of exogenous <protein>TNF</protein> to the <cell_line>intermediate thymocyte cultures</cell_line> induces <protein>NF-kappaB</protein> activity and is sufficient to promote HIV replication in the cocultures with <cell_type>TEC</cell_type> .


The other major subpopulation expressing the CD4 receptor , namely , the double-positive ( DP ) CD4 ( + ) CD8 ( + ) CD3 ( +/- ) thymocytes , despite the entry of the virus , do not produce a significant level of virus , presumably because they are unresponsive to TNF and IL-7 .

The other major subpopulation expressing the <protein>CD4 receptor</protein> , namely , the <cell_type>double-positive ( DP ) CD4 ( + ) CD8 ( + ) CD3 ( +/- ) thymocytes</cell_type> , despite the entry of the virus , do not produce a significant level of virus , presumably because they are unresponsive to <protein>TNF</protein> and <protein>IL-7</protein> .


Together , these data suggest that in vivo , despite an efficient entry of the virus in all the CD4 ( + ) subpopulations , a high viral load may be generated exclusively within the mature CD4 ( + ) CD8 ( - ) CD3 ( + ) subset of thymocytes .

Together , these data suggest that in vivo , despite an efficient entry of the virus in all the <cell_type>CD4 ( + ) subpopulations</cell_type> , a high viral load may be generated exclusively within the <cell_type>mature CD4 ( + ) CD8 ( - ) CD3 ( + ) subset of thymocytes</cell_type> .


However , under conditions of inflammatory response after infection , TNF might also be present in the intermediate thymocyte compartment , leading to efficient HIV replication in these cells .

However , under conditions of inflammatory response after infection , <protein>TNF</protein> might also be present in the <cell_type>intermediate thymocyte compartment</cell_type> , leading to efficient HIV replication in these cells .


NF-kappaB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes .

<cell_type>NF-kappaB-mediated up-regulation</cell_type> of <protein>Bcl-x</protein> and <protein>Bfl-1/A1</protein> is required for <protein>CD40</protein> survival signaling in <cell_type>B lymphocytes</cell_type> .


Activation of CD40 is essential for thymus-dependent humoral immune responses and rescuing B cells from apoptosis .

Activation of <protein>CD40</protein> is essential for thymus-dependent humoral immune responses and rescuing <cell_type>B cells</cell_type> from apoptosis .


Many of the effects of CD40 are believed to be achieved through altered gene expression .

Many of the effects of <protein>CD40</protein> are believed to be achieved through altered gene expression .


In addition to Bcl-x , a known CD40-regulated antiapoptotic molecule , we identified a related antiapoptotic molecule , A1/Bfl-1 , as a CD40-inducible gene .

In addition to <protein>Bcl-x</protein> , a known <protein>CD40-regulated antiapoptotic molecule</protein> , we identified a related <protein>antiapoptotic molecule</protein> , <protein>A1/Bfl-1</protein> , as a <dna>CD40-inducible gene</dna> .


Inhibition of the NF-kappaB pathway by overexpression of a dominant-active inhibitor of NF-kappaB abolished CD40 -induced up-regulation of both the Bfl-1 and Bcl-x genes and also eliminated the ability of CD40 to rescue Fas -induced cell death .

Inhibition of the <protein>NF-kappaB</protein> pathway by overexpression of a dominant-active inhibitor of <protein>NF-kappaB</protein> abolished <protein>CD40</protein> -induced up-regulation of both the <protein>Bfl-1</protein> and <protein>Bcl-x</protein> genes and also eliminated the ability of <protein>CD40</protein> to rescue <protein>Fas</protein> -induced cell death .


Within the upstream promoter region of Bcl-x , a potential NF-kappaB-binding sequence was found to support NF-kappaB -dependent transcriptional activation .

Within the <dna>upstream promoter region</dna> of <protein>Bcl-x</protein> , a potential <dna>NF-kappaB-binding sequence</dna> was found to support <protein>NF-kappaB</protein> -dependent transcriptional activation .


Furthermore , expression of physiological levels of Bcl-x protected B cells from Fas-mediated apoptosis in the absence of NF-kappaB signaling .

Furthermore , expression of physiological levels of <cell_type>Bcl-x protected B cells</cell_type> from Fas-mediated apoptosis in the absence of <protein>NF-kappaB</protein> signaling .


Thus , our results suggest that CD40 -mediated cell survival proceeds through NF-kappaB -dependent up-regulation of Bcl-2 family members .

Thus , our results suggest that <protein>CD40</protein> -mediated cell survival proceeds through <protein>NF-kappaB</protein> -dependent up-regulation of <protein>Bcl-2 family members</protein> .


Stimulation of neutrophil interleukin-8 production by eosinophil granule major basic protein .

Stimulation of <cell_type>neutrophil</cell_type> <protein>interleukin-8</protein> production by <protein>eosinophil granule major basic protein</protein> .


We evaluated the ability of eosinophil granule major basic protein ( MBP ) to stimulate interleukin ( IL ) -8 production by neutrophils .

We evaluated the ability of <protein>eosinophil granule major basic protein</protein> ( <protein>MBP</protein> ) to stimulate <protein>interleukin ( IL ) -8</protein> production by <cell_type>neutrophils</cell_type> .


MBP over the concentration range of 0.1 to 10 microM stimulated the release of up to approximately 8 ng/ml IL-8 .

<protein>MBP</protein> over the concentration range of 0.1 to 10 microM stimulated the release of up to approximately 8 ng/ml <protein>IL-8</protein> .


Incubation with 2 microM MBP showed that , after a 1 h lag , the level of IL-8 release increased with time for approximately 10 h .

Incubation with 2 microM <protein>MBP</protein> showed that , after a 1 h lag , the level of <protein>IL-8</protein> release increased with time for approximately 10 h .


At the 2 microM concentration , eosinophil cationic protein , eosinophil-derived neurotoxin , and eosinophil peroxidase did not stimulate significant levels of IL-8 production .

At the 2 microM concentration , <protein>eosinophil cationic protein</protein> , eosinophil-derived neurotoxin , and <protein>eosinophil peroxidase</protein> did not stimulate significant levels of <protein>IL-8</protein> production .


MBP stimulated 2-fold increases in IL-8 messenger RNA ( mRNA ) after 1 and 3 h of incubation , which were blocked by pretreatment with actinomycin D .

<protein>MBP</protein> stimulated 2-fold increases in <rna>IL-8 messenger RNA</rna> ( <rna>mRNA</rna> ) after 1 and 3 h of incubation , which were blocked by pretreatment with actinomycin D .


However , stimulation with MBP did not produce an increase in the binding activity of nuclear factor ( NF ) -kappaB or activator protein-1 .

However , stimulation with <protein>MBP</protein> did not produce an increase in the binding activity of <protein>nuclear factor ( NF ) -kappaB</protein> or <protein>activator protein-1</protein> .


No NF-IL-6 binding activity was detected in the same nuclear extracts .

No <protein>NF-IL-6</protein> binding activity was detected in the same nuclear extracts .


In addition , stimulation with MBP prolonged the stability of IL-8 mRNA .

In addition , stimulation with <protein>MBP</protein> prolonged the stability of <rna>IL-8 mRNA</rna> .


MBP also induced transient increases in mRNA for macrophage inflammatory protein ( MIP ) -1alpha and MIP-1beta , but did not stimulate the release of either chemokine .

<protein>MBP</protein> also induced transient increases in <rna>mRNA</rna> for <protein>macrophage inflammatory protein ( MIP ) -1alpha</protein> and <protein>MIP-1beta</protein> , but did not stimulate the release of either <protein>chemokine</protein> .


These findings indicate that MBP is selective among the eosinophil granule proteins as a stimulus for neutrophil IL-8 release and , further , that stimulation of neutrophil IL-8 release by MBP involves both transcriptional and posttranscriptional regulation .

These findings indicate that <protein>MBP</protein> is selective among the <protein>eosinophil granule proteins</protein> as a stimulus for <cell_type>neutrophil</cell_type> <protein>IL-8</protein> release and , further , that stimulation of <cell_type>neutrophil</cell_type> <protein>IL-8</protein> release by <protein>MBP</protein> involves both transcriptional and posttranscriptional regulation .