Since HUVECs released superoxide anions in response to TNF , and H2O2 induces VCAM-1 , PDTC may act as a radical scavenger .

Since <cell_line>HUVECs</cell_line> released superoxide anions in response to TNF , and H2O2 induces <protein>VCAM-1</protein> , PDTC may act as a radical scavenger .


Although ICAM-1 induction was unaffected , inhibitors of NADPH oxidase ( apocynin ) or cytochrome P-450 ( SKF525a ) suppressed VCAM-1 induction by TNF , revealing that several radical-generating systems are involved in its regulation .

Although <protein>ICAM-1</protein> induction was unaffected , inhibitors of <protein>NADPH oxidase</protein> ( apocynin ) or <protein>cytochrome P-450</protein> ( SKF525a ) suppressed <protein>VCAM-1</protein> induction by TNF , revealing that several radical-generating systems are involved in its regulation .


PDTC , apocynin , or SKF525a decreased adhesion of monocytic U937 cells to TNF-treated HUVECs ( by 75 % at 100 mumol/L PDTC ) .

PDTC , apocynin , or SKF525a decreased adhesion of <cell_line>monocytic U937 cells</cell_line> to <cell_line>TNF-treated HUVECs</cell_line> ( by 75 % at 100 mumol/L PDTC ) .


Inhibition by anti-VCAM-1 monoclonal antibody 1G11 indicated that U937 adhesion was VCAM-1 dependent and suppression by antioxidants was due to reduced VCAM-1 induction .

Inhibition by <protein>anti-VCAM-1 monoclonal antibody</protein> <protein>1G11</protein> indicated that <cell_line>U937</cell_line> adhesion was <protein>VCAM-1</protein> dependent and suppression by antioxidants was due to reduced <protein>VCAM-1</protein> induction .


( ABSTRACT TRUNCATED AT 250 WORDS )


Displacement of an E-box-binding repressor by basic helix-loop-helix proteins : implications for B-cell specificity of the immunoglobulin heavy-chain enhancer .

Displacement of an <protein>E-box-binding repressor</protein> by <protein>basic helix-loop-helix proteins</protein> : implications for B-cell specificity of the <dna>immunoglobulin heavy-chain enhancer</dna> .


The activity of the immunoglobulin heavy-chain ( IgH ) enhancer is restricted to B cells , although it binds both B-cell-restricted and ubiquitous transcription factors .

The activity of the <dna>immunoglobulin heavy-chain ( IgH ) enhancer</dna> is restricted to <cell_type>B cells</cell_type> , although it binds both <protein>B-cell-restricted and ubiquitous transcription factors</protein> .


Activation of the enhancer in non-B cells upon overexpression of the basic helix-loop-helix ( bHLH ) protein E2A appears to be mediated not only by the binding of E2A to its cognate E box but also by the resulting displacement of a repressor from that same site .

Activation of the <dna>enhancer</dna> in <cell_type>non-B cells</cell_type> upon overexpression of the <protein>basic helix-loop-helix ( bHLH ) protein</protein> <protein>E2A</protein> appears to be mediated not only by the binding of <protein>E2A</protein> to its cognate <dna>E box</dna> but also by the resulting displacement of a <protein>repressor</protein> from that same site .


We have identified a `` two-handed '' zinc finger protein , denoted ZEB , the DNA-binding specificity of which mimics that of the cellular repressor .

We have identified a <protein>`` two-handed '' zinc finger protein</protein> , denoted <protein>ZEB</protein> , the DNA-binding specificity of which mimics that of the <protein>cellular repressor</protein> .


By employing a derivative E box that binds ZEB but not E2A , we have shown that the repressor is active in B cells and the IgH enhancer is silenced in the absence of binding competition by bHLH proteins .

By employing a derivative <dna>E box</dna> that binds <protein>ZEB</protein> but not <protein>E2A</protein> , we have shown that the <protein>repressor</protein> is active in <cell_type>B cells</cell_type> and the <dna>IgH enhancer</dna> is silenced in the absence of binding competition by <protein>bHLH proteins</protein> .


Hence , we propose that a necessary prerequisite of enhancer activity is the B-cell-specific displacement of a ZEB-like repressor by bHLH proteins .

Hence , we propose that a necessary prerequisite of <dna>enhancer</dna> activity is the B-cell-specific displacement of a <protein>ZEB-like repressor</protein> by <protein>bHLH proteins</protein> .


Inhibition of NF-kappa B by sodium salicylate and aspirin [ see comments ]

Inhibition of <protein>NF-kappa B</protein> by sodium salicylate and aspirin [ see comments ]


The transcription factor nuclear factor-kappa B ( NF-kappa B ) is critical for the inducible expression of multiple cellular and viral genes involved in inflammation and infection including interleukin-1 ( IL-1 ) , IL-6 , and adhesion molecules .

The <protein>transcription factor</protein> <protein>nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) is critical for the inducible expression of multiple <dna>cellular and viral genes</dna> involved in inflammation and infection including <protein>interleukin-1</protein> ( <protein>IL-1</protein> ) , <protein>IL-6</protein> , and <protein>adhesion molecules</protein> .


The anti-inflammatory drugs sodium salicylate and aspirin inhibited the activation of NF-kappa B , which further explains the mechanism of action of these drugs .

The anti-inflammatory drugs sodium salicylate and aspirin inhibited the activation of <protein>NF-kappa B</protein> , which further explains the mechanism of action of these drugs .


This inhibition prevented the degradation of the NF-kappa B inhibitor , I kappa B , and therefore NF-kappa B was retained in the cytosol .

This inhibition prevented the degradation of the <protein>NF-kappa B inhibitor</protein> , <protein>I kappa B</protein> , and therefore <protein>NF-kappa B</protein> was retained in the cytosol .


Sodium salicylate and aspirin also inhibited NF-kappa B -dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus ( HIV ) long terminal repeat ( LTR ) in transfected T cells .

Sodium salicylate and aspirin also inhibited <protein>NF-kappa B</protein> -dependent transcription from the <dna>Ig kappa enhancer</dna> and the <dna>human immunodeficiency virus ( HIV ) long terminal repeat</dna> ( <dna>LTR</dna> ) in <cell_line>transfected T cells</cell_line> .


Effects of the antisense myb expression on hemin- and erythropoietin- induced erythroid differentiation of K562 cells .

Effects of the antisense myb expression on hemin- and erythropoietin- induced erythroid differentiation of <cell_line>K562 cells</cell_line> .


In order to elucidate the role of c-myb gene in erythroid differentiation of K562 cell induced by hemin ( Hm ) and erythropoietin ( Epo ) , we constructed recombinant plasmid that could produce antisense myb RNA after induction with dexamethasone .

In order to elucidate the role of <dna>c-myb gene</dna> in erythroid differentiation of <cell_line>K562 cell</cell_line> induced by <protein>hemin</protein> ( <protein>Hm</protein> ) and <protein>erythropoietin</protein> ( <protein>Epo</protein> ) , we constructed <dna>recombinant plasmid</dna> that could produce <rna>antisense myb RNA</rna> after induction with dexamethasone .


During treatment with Hm , K562 cells constitutively expressed c-myb mRNA , and 50 % of them began to synthesize hemoglobin ( Hb ) .

During treatment with <protein>Hm</protein> , <cell_line>K562 cells</cell_line> constitutively expressed <rna>c-myb mRNA</rna> , and 50 % of them began to synthesize <protein>hemoglobin</protein> ( <protein>Hb</protein> ) .


Expression of antisense myb RNA reduced the amount of c-myb mRNA , and the percentage of Hb-synthesizing cells was decreased to 20 % .

Expression of <rna>antisense myb RNA</rna> reduced the amount of <rna>c-myb mRNA</rna> , and the percentage of <cell_line>Hb-synthesizing cells</cell_line> was decreased to 20 % .


In the presence of Epo , c-myb mRNA declined and 20 % of K562 cells synthesized Hb regardless of antisense myb RNA expression .

In the presence of <protein>Epo</protein> , <rna>c-myb mRNA</rna> declined and 20 % of <cell_line>K562 cells</cell_line> synthesized <protein>Hb</protein> regardless of <rna>antisense myb RNA</rna> expression .


It is suggested that constitutive expression of c-myb mRNA is necessary for Hm -induced differentiation , and that a decrease in the amount of c-myb mRNA induced by antisense myb RNA expression suppresses Hm -induced differentiation .

It is suggested that constitutive expression of <rna>c-myb mRNA</rna> is necessary for <protein>Hm</protein> -induced differentiation , and that a decrease in the amount of <rna>c-myb mRNA</rna> induced by <rna>antisense myb RNA</rna> expression suppresses <protein>Hm</protein> -induced differentiation .


The amount of c-myb mRNA in K562 cells was reduced during the differentiation induced by Epo .

The amount of <rna>c-myb mRNA</rna> in <cell_line>K562 cells</cell_line> was reduced during the differentiation induced by <protein>Epo</protein> .


Expression of GATA-1 mRNA was almost constant during Hm -induced differentiation , but increased during Epo treatment .

Expression of <rna>GATA-1 mRNA</rna> was almost constant during <protein>Hm</protein> -induced differentiation , but increased during <protein>Epo</protein> treatment .


It is supposed that the mechanism of Hm -induced differentiation is distinguished from that of Epo -induced differentiation in K562 cells .

It is supposed that the mechanism of <protein>Hm</protein> -induced differentiation is distinguished from that of <protein>Epo</protein> -induced differentiation in <cell_line>K562 cells</cell_line> .


Prenatal immune challenge alters the hypothalamic-pituitary-adrenocortical axis in adult rats .


We investigated whether non-abortive maternal infections would compromise fetal brain development and alter hypothalamic-pituitary-adrenocortical ( HPA ) axis functioning when adult .


To study putative teratogenic effects of a T cell-mediated immune response versus an endotoxic challenge , 10-d-pregnant rats received a single intraperitoneal injection of 5 x 10 ( 8 ) human red blood cells ( HRBC ) or gram-negative bacterial endotoxin ( Escherichia coli LPS : 30 micrograms/kg ) .

To study putative teratogenic effects of a T cell-mediated immune response versus an endotoxic challenge , 10-d-pregnant rats received a single intraperitoneal injection of 5 x 10 ( 8 ) <cell_type>human red blood cells</cell_type> ( <cell_type>HRBC</cell_type> ) or gram-negative bacterial endotoxin ( Escherichia coli LPS : 30 micrograms/kg ) .


The adult male progeny ( 3 mo old ) of both experimental groups showed increased basal plasma corticosterone levels .


In addition , after novelty stress the HRBC group , but not the LPS group , showed increased ACTH and corticosterone levels .

In addition , after novelty stress the <cell_type>HRBC</cell_type> group , but not the <cell_line>LPS group</cell_line> , showed increased ACTH and corticosterone levels .


Both groups showed substantial decreases in mineralocorticoid ( MR ) and glucocorticoid receptor ( GR ) levels in the hippocampus , a limbic brain structure critical for HPA axis regulation , whereas GR concentrations in the hypothalamus were unchanged and in anterior pituitary were slightly increased .

Both groups showed substantial decreases in mineralocorticoid ( MR ) and glucocorticoid receptor ( GR ) levels in the hippocampus , a limbic brain structure critical for HPA axis regulation , whereas <protein>GR</protein> concentrations in the hypothalamus were unchanged and in anterior pituitary were slightly increased .


HRBC and LPS indeed stimulated the maternal immune system as revealed by specific anti-HRBC antibody production and enhanced IL-1 beta mRNA expression in splenocytes , respectively .

<cell_type>HRBC</cell_type> and LPS indeed stimulated the maternal immune system as revealed by specific <protein>anti-HRBC antibody</protein> production and enhanced IL-1 beta mRNA expression in <cell_type>splenocytes</cell_type> , respectively .


This study demonstrates that a T cell-mediated immune response as well as an endotoxic challenge during pregnancy can induce anomalies in HPA axis function in adulthood .


Clinically , it may be postulated that disturbed fetal brain development due to prenatal immune challenge increases the vulnerability to develop mental illness involving inadequate responses to stress .


A low NM23.H1 gene expression identifying high malignancy human melanomas .

A low <dna>NM23.H1 gene</dna> expression identifying high malignancy human melanomas .


The NM23 gene has been proposed as a metastasis-suppressor gene , and its use has been suggested as prognostic factor .

The <dna>NM23 gene</dna> has been proposed as a <dna>metastasis-suppressor gene</dna> , and its use has been suggested as prognostic factor .


NM23 was identified in a system of murine melanoma cell lines , in which an inverse relationship was found between NM23 expression and metastatic ability .

<protein>NM23</protein> was identified in a system of <cell_line>murine melanoma cell lines</cell_line> , in which an inverse relationship was found between <protein>NM23</protein> expression and metastatic ability .


In a human malignant melanoma study NM23 expression was found to be significantly lower in metastases that developed less than 24 months after diagnosis of the primary tumours .

In a human malignant melanoma study <protein>NM23</protein> expression was found to be significantly lower in metastases that developed less than 24 months after diagnosis of the primary tumours .


The present paper studies the expression of the NM23.H1 gene in cell lines which derive from primary or metastatic human malignant melanomas in relation to staging , infiltration degree , lymphocytic infiltration , cell morphology , cell pigmentation , karyotype , and disease-free survival .

The present paper studies the expression of the <dna>NM23.H1 gene</dna> in <cell_line>cell lines</cell_line> which derive from primary or metastatic human malignant melanomas in relation to staging , infiltration degree , lymphocytic infiltration , cell morphology , cell pigmentation , karyotype , and disease-free survival .


The level of mRNA expression of the NM23 gene is significantly lower in cell lines that derive from more infiltrating primary melanomas than in cell lines obtained from less infiltrating tumours .

The level of mRNA expression of the <dna>NM23 gene</dna> is significantly lower in <cell_line>cell lines</cell_line> that derive from more infiltrating primary melanomas than in <cell_line>cell lines</cell_line> obtained from less infiltrating tumours .


Moreover , cell lines derived from tumours of patients with a disease-free survival of more than 24 months ( 24-58 months ) express the NM23 gene at higher levels than cell lines obtained from melanomas of patients with a disease-free survival of less than 24 months ( 6-15 months ) .

Moreover , <cell_line>cell lines</cell_line> derived from tumours of patients with a disease-free survival of more than 24 months ( 24-58 months ) express the <dna>NM23 gene</dna> at higher levels than <cell_line>cell lines</cell_line> obtained from melanomas of patients with a disease-free survival of less than 24 months ( 6-15 months ) .


Activation of a novel serine/threonine kinase that phosphorylates c-Fos upon stimulation of T and B lymphocytes via antigen and cytokine receptors .

Activation of a novel <protein>serine/threonine kinase</protein> that phosphorylates <protein>c-Fos</protein> upon stimulation of <cell_type>T and B lymphocytes</cell_type> via antigen and <protein>cytokine receptors</protein> .


Ligation of Ag receptors in T and B lymphocytes initiates signal transduction cascades which alter the expression of genes that regulate cellular proliferation and differentiation .

Ligation of <protein>Ag receptors</protein> in <cell_type>T and B lymphocytes</cell_type> initiates signal transduction cascades which alter the expression of genes that regulate cellular proliferation and differentiation .


The transmission of signals from the membrane to the nucleus is mediated principally through the action of protein tyrosine and serine/threonine kinases .

The transmission of signals from the membrane to the nucleus is mediated principally through the action of <protein>protein tyrosine and serine/threonine kinases</protein> .


We have identified and characterized a novel serine/threonine kinase that phosphorylated the proto-oncogene product , c-Fos , and is termed Fos kinase .

We have identified and characterized a novel <protein>serine/threonine kinase</protein> that phosphorylated the <protein>proto-oncogene product</protein> , <protein>c-Fos</protein> , and is termed <protein>Fos kinase</protein> .


Fos kinase was rapidly activated after ligation of the CD3 and CD2 receptors in Jurkat and normal human T lymphocytes and in response to IL-6 and anti-IgM in the human B cell lines AF10 and Ramos , respectively .

<protein>Fos kinase</protein> was rapidly activated after ligation of the <protein>CD3 and CD2 receptors</protein> in <cell_line>Jurkat</cell_line> and <cell_type>normal human T lymphocytes</cell_type> and in response to <protein>IL-6</protein> and <protein>anti-IgM</protein> in the <cell_line>human B cell lines</cell_line> <cell_line>AF10</cell_line> and <cell_line>Ramos</cell_line> , respectively .


The phorbol ester , PMA , was also a potent inducer of Fos kinase activity in all of the above populations , suggesting that PKC plays a role in the regulation of this enzyme .

The phorbol ester , PMA , was also a potent inducer of <protein>Fos kinase</protein> activity in all of the above populations , suggesting that <protein>PKC</protein> plays a role in the regulation of this <protein>enzyme</protein> .


Fos kinase phosphorylates c-Fos at a site near the C-terminus , as well as a peptide derived from this region ( residues 359-370 , RKGSSSNEPSSD ) , and Fos peptide competitively inhibited c-Fos phosphorylation .

<protein>Fos kinase</protein> phosphorylates <protein>c-Fos</protein> at a site near the <protein>C-terminus</protein> , as well as a peptide derived from this region ( <protein>residues 359-370</protein> , <protein>RKGSSSNEPSSD</protein> ) , and Fos peptide competitively inhibited <protein>c-Fos</protein> phosphorylation .


Fos kinase was shown to be distinct from other identified serine/threonine kinases , including protein kinase A , protein kinase C , casein kinase II , MAP kinases , p70S6K and p90RSK .

<protein>Fos kinase</protein> was shown to be distinct from other identified <protein>serine/threonine kinases</protein> , including <protein>protein kinase A</protein> , <protein>protein kinase C</protein> , <protein>casein kinase II</protein> , <protein>MAP kinases</protein> , <protein>p70S6K</protein> and <protein>p90RSK</protein> .


Fos kinase was purified by anion exchange chromatography and exhibited an apparent M ( r ) = 65 , 000 and isoelectric point = 6.1 .

<protein>Fos kinase</protein> was purified by anion exchange chromatography and exhibited an apparent M ( r ) = 65 , 000 and isoelectric point = 6.1 .


Fos kinase may play a role in transcriptional regulation through its capacity to phosphorylate c-Fos at a site required for expression of the transcriptional transrepressive activity of this molecule .

<protein>Fos kinase</protein> may play a role in transcriptional regulation through its capacity to phosphorylate <protein>c-Fos</protein> at a site required for expression of the transcriptional transrepressive activity of this molecule .


Moreover , its rapid activation suggests it may have a wider role within signal transduction cascades in lymphocytes .

Moreover , its rapid activation suggests it may have a wider role within signal transduction cascades in <cell_type>lymphocytes</cell_type> .


Antigenic specificities of human CD4+ T-cell clones recovered from recurrent genital herpes simplex virus type 2 lesions .

Antigenic specificities of <cell_line>human CD4+ T-cell clones</cell_line> recovered from recurrent genital herpes simplex virus type 2 lesions .


Lesions resulting from recurrent genital herpes simplex virus ( HSV ) infection are characterized by infiltration of CD4+ lymphocytes .

Lesions resulting from recurrent genital herpes simplex virus ( HSV ) infection are characterized by infiltration of <cell_type>CD4+ lymphocytes</cell_type> .


We have investigated the antigenic specificity of 47 HSV-specific CD4+ T-cell clones recovered from the HSV-2 buttock and thigh lesions of five patients .

We have investigated the antigenic specificity of 47 <cell_line>HSV-specific CD4+ T-cell clones</cell_line> recovered from the HSV-2 buttock and thigh lesions of five patients .


Clones with proliferative responses to recombinant truncated glycoprotein B ( gB ) or gD of HSV-2 or purified natural gC of HSV-2 comprised a minority of the total number of HSV-specific clones isolated from lesions .

Clones with proliferative responses to <protein>recombinant truncated glycoprotein B</protein> ( <protein>gB</protein> ) or <protein>gD</protein> of HSV-2 or purified natural gC of HSV-2 comprised a minority of the total number of <cell_line>HSV-specific clones</cell_line> isolated from lesions .


The gC2- and gD2-specific CD4+ clones had cytotoxic activity .

The <cell_line>gC2- and gD2-specific CD4+ clones</cell_line> had cytotoxic activity .


The approximate locations of the HSV-2 genes encoding HSV-2 type-specific CD4+ antigens have been determined by using HSV-1 x HSV-2 intertypic recombinant virus and include the approximate map regions 0.30 to 0.46 , 0.59 to 0.67 , 0.67 to 0.73 , and 0.82 to 1.0 units .

The approximate locations of the HSV-2 genes encoding HSV-2 type-specific <protein>CD4+ antigens</protein> have been determined by using HSV-1 x HSV-2 intertypic recombinant virus and include the approximate map regions 0.30 to 0.46 , 0.59 to 0.67 , 0.67 to 0.73 , and 0.82 to 1.0 units .


The antigenic specificity of an HLA DQ2-restricted , HSV-2 type-specific T-cell clone was mapped to amino acids 425 to 444 of VP16 of HSV-2 by sequential use of an intertypic recombinant virus containing VP16 of HSV-2 in an HSV-1 background , recombinant VP16 fusion proteins , and synthetic peptides .

The antigenic specificity of an <cell_line>HLA DQ2-restricted , HSV-2 type-specific T-cell clone</cell_line> was mapped to <protein>amino acids 425 to 444</protein> of <protein>VP16</protein> of HSV-2 by sequential use of an intertypic recombinant virus containing <protein>VP16</protein> of HSV-2 in an HSV-1 background , <protein>recombinant VP16 fusion proteins</protein> , and synthetic peptides .


Each of the remaining four patients also yielded at least one type-specific T-cell clone reactive with an HSV-2 epitope mapping to approximately 0.67 to 0.73 map units .

Each of the remaining four patients also yielded at least one <cell_line>type-specific T-cell clone</cell_line> reactive with an HSV-2 epitope mapping to approximately 0.67 to 0.73 map units .


The antigenic specificities of lesion-derived CD4+ T-cell clones are quite diverse and include at least 10 epitopes .

The antigenic specificities of <cell_line>lesion-derived CD4+ T-cell clones</cell_line> are quite diverse and include at least 10 epitopes .


Human T-cell clones reactive with gC and VP16 are reported here for the first time .

<cell_line>Human T-cell clones</cell_line> reactive with <protein>gC</protein> and <protein>VP16</protein> are reported here for the first time .


Marked basophilia in acute promyelocytic leukaemia treated with all-trans retinoic acid : molecular analysis of the cell origin of the basophils .

Marked basophilia in acute promyelocytic leukaemia treated with all-trans retinoic acid : molecular analysis of the cell origin of the <cell_type>basophils</cell_type> .


We report a patient with acute promyelocytic leukaemia who developed marked basophilia during all-trans retinoic acid treatment .


We studied genomic DNA and RNA extracted from the patient 's peripheral leucocytes in order to determine the origin of the basophils .

We studied <dna>genomic DNA</dna> and RNA extracted from the patient 's <cell_type>peripheral leucocytes</cell_type> in order to determine the origin of the <cell_type>basophils</cell_type> .


The RAR alpha rearranged band in the Southern blot analysis and a chimaeric product of PML-RAR alpha by polymerase chain reaction were strongly visible before ATRA treatment , but at the time of maximal basophilia both of them were markedly diminished .

The <protein>RAR alpha</protein> rearranged band in the Southern blot analysis and a <protein>chimaeric product</protein> of <protein>PML-RAR alpha</protein> by polymerase chain reaction were strongly visible before ATRA treatment , but at the time of maximal basophilia both of them were markedly diminished .


These findings suggest that the basophils which appeared during the ATRA treatment are reactive in nature rather than a leukaemic clone .

These findings suggest that the <cell_type>basophils</cell_type> which appeared during the ATRA treatment are reactive in nature rather than a <cell_line>leukaemic clone</cell_line> .


Activation of the interleukin 6 gene by Mycobacterium tuberculosis or lipopolysaccharide is mediated by nuclear factors NF-IL6 and NF-kappa B [ published erratum appears in Proc Natl Acad Sci U S A 1995 Apr 11 ; 92 ( 8 ) : 3632 ]

Activation of the <dna>interleukin 6 gene</dna> by Mycobacterium tuberculosis or lipopolysaccharide is mediated by <protein>nuclear factors NF-IL6</protein> and <protein>NF-kappa B</protein> [ published erratum appears in Proc Natl Acad Sci U S A 1995 Apr 11 ; 92 ( 8 ) : 3632 ]


The host response to Mycobacterium tuberculosis includes granuloma formation at sites of infection and systemic symptoms .


Cytokines have been identified by immunohistochemistry in granulomas in animal models of bacillus Calmette-Guerin ( BCG ) infection and are released by mononuclear phagocytes upon stimulation by mycobacterial proteins .

<protein>Cytokines</protein> have been identified by immunohistochemistry in granulomas in animal models of bacillus Calmette-Guerin ( BCG ) infection and are released by <cell_type>mononuclear phagocytes</cell_type> upon stimulation by mycobacterial proteins .


In this regard , the cytokine interleukin 6 ( IL-6 ) may play a role in the clinical manifestations and pathological events of tuberculosis infection .

In this regard , the <protein>cytokine</protein> <protein>interleukin 6</protein> ( <protein>IL-6</protein> ) may play a role in the clinical manifestations and pathological events of tuberculosis infection .


We have demonstrated that lipoarabinomannan ( LAM ) from the mycobacterial cell wall , which was virtually devoid of lipopolysaccharide ( LPS ) , stimulated mononuclear phagocytes to release IL-6 in a dose-response manner .

We have demonstrated that <protein>lipoarabinomannan</protein> ( <protein>LAM</protein> ) from the mycobacterial cell wall , which was virtually devoid of lipopolysaccharide ( LPS ) , stimulated <cell_type>mononuclear phagocytes</cell_type> to release <protein>IL-6</protein> in a dose-response manner .


LAM and LPS were potent inducers of IL-6 gene expression in peripheral blood monocytes .

<protein>LAM</protein> and LPS were potent inducers of <dna>IL-6 gene</dna> expression in <cell_type>peripheral blood monocytes</cell_type> .


Both LAM -and LPS-inducible IL-6 promoter activity was localized to a DNA fragment , positions -158 to -49 , by deletion analysis and chloramphenicol acetyltransferase assay .

Both <protein>LAM</protein> -and <dna>LPS-inducible IL-6 promoter</dna> activity was localized to a <dna>DNA fragment</dna> , positions <dna>-158 to -49</dna> , by deletion analysis and <protein>chloramphenicol acetyltransferase</protein> assay .


Two nuclear factor NF-IL6 ( positions -153 to -145 and -83 to -75 ) and one nuclear factor NF-kappa B ( positions -72 to -63 ) motifs are present within this fragment .

Two <protein>nuclear factor NF-IL6</protein> ( positions <dna>-153 to -145</dna> and -83 to -75 ) and one <dna>nuclear factor NF-kappa B ( positions -72 to -63 ) motifs</dna> are present within this fragment .


Site-directed mutagenesis of one or more of these motifs within the IL-6 promoter demonstrated that each has positive regulatory activity and that they could act in a function- and orientation-independent manner .

Site-directed mutagenesis of one or more of these motifs within the <protein>IL-6</protein> promoter demonstrated that each has positive regulatory activity and that they could act in a function- and orientation-independent manner .


Deletion of all three elements abolished inducibility of IL-6 promoter activity by both LAM and LPS .

Deletion of all three elements abolished inducibility of <dna>IL-6 promoter</dna> activity by both <protein>LAM</protein> and LPS .


We conclude that the NF-IL6 and NF-kappa B sites mediate IL-6 induction in response to both LPS and LAM , acting as bacterial or mycobacterial response elements .

We conclude that the <dna>NF-IL6 and NF-kappa B sites</dna> mediate <protein>IL-6</protein> induction in response to both LPS and <protein>LAM</protein> , acting as <dna>bacterial or mycobacterial response elements</dna> .


Regulation of CD14 expression during monocytic differentiation induced with 1 alpha , 25-dihydroxyvitamin D3 .

Regulation of <protein>CD14</protein> expression during monocytic differentiation induced with 1 alpha , 25-dihydroxyvitamin D3 .


CD14 , a monocyte/macrophage receptor for the complex of LPS and LPS binding protein , is a differentiation marker for the monocyte/macrophage lineage .

<protein>CD14</protein> , a <protein>monocyte/macrophage receptor</protein> for the complex of LPS and <protein>LPS binding protein</protein> , is a differentiation marker for the <cell_type>monocyte/macrophage lineage</cell_type> .


We have analyzed the regulation of CD14 expression during 1 alpha , 25-dihydroxyvitamin D3 ( VitD3 ) -induced monocytic differentiation .

We have analyzed the regulation of <protein>CD14</protein> expression during 1 alpha , 25-dihydroxyvitamin D3 ( VitD3 ) -induced monocytic differentiation .


Using FACS , Northern blotting , and nuclear run-on analyses , we demonstrate that the up-regulation of CD14 expression during monocytic cell maturation is regulated mainly at the level of gene transcription , and that new protein synthesis is required for CD14 induction .

Using FACS , Northern blotting , and nuclear run-on analyses , we demonstrate that the up-regulation of <protein>CD14</protein> expression during monocytic cell maturation is regulated mainly at the level of gene transcription , and that new protein synthesis is required for <protein>CD14</protein> induction .


We have recently cloned the CD14 5 ' upstream sequence and demonstrated its tissue-specific promoter activity .

We have recently cloned the <dna>CD14 5 ' upstream sequence</dna> and demonstrated its <dna>tissue-specific promoter</dna> activity .


Using stable transfection of the monocytoid U937 cell line with a series of deletion mutants of the CD14 5 ' upstream sequence coupled to a reporter gene construct , we show that bp -128 to -70 is the critical region for the induction of CD14 expression .

Using stable transfection of the <cell_line>monocytoid U937 cell line</cell_line> with a series of deletion mutants of the <dna>CD14 5 ' upstream sequence</dna> coupled to a reporter gene construct , we show that <dna>bp -128 to -70</dna> is the critical region for the induction of <protein>CD14</protein> expression .


This region contains two binding sites for the Sp1 transcription factor .

This region contains two <dna>binding sites</dna> for the <protein>Sp1 transcription factor</protein> .


A 3-bp mutation at the distal Sp1-binding site not only eliminates Sp1 interaction , but also abolishes most of the VitD3 induction of CD14 expression .

A 3-bp mutation at the distal <dna>Sp1-binding site</dna> not only eliminates <protein>Sp1</protein> interaction , but also abolishes most of the VitD3 induction of <protein>CD14</protein> expression .


Electrophoretic mobility shift analysis does not detect a direct interaction of the CD14 distal Sp1-binding site with the vitamin D3 receptor and its partner , the retinoid X receptor .

Electrophoretic mobility shift analysis does not detect a direct interaction of the <protein>CD14</protein> distal <dna>Sp1-binding site</dna> with the <protein>vitamin D3 receptor</protein> and its partner , the <protein>retinoid X receptor</protein> .


These data demonstrate that VitD3 induces CD14 indirectly through some intermediary factor , and suggest a critical role for Sp1 in this process .

These data demonstrate that VitD3 induces <protein>CD14</protein> indirectly through some <protein>intermediary factor</protein> , and suggest a critical role for <protein>Sp1</protein> in this process .


DNA-binding and transcriptional regulatory properties of hepatic leukemia factor ( HLF ) and the t ( 17 ; 19 ) acute lymphoblastic leukemia chimera E2A-HLF .

DNA-binding and transcriptional regulatory properties of <protein>hepatic leukemia factor</protein> ( <protein>HLF</protein> ) and the t ( 17 ; 19 ) <protein>acute lymphoblastic leukemia chimera E2A-HLF</protein> .


The t ( 17 ; 19 ) translocation in acute lymphoblastic leukemias results in creation of E2A-hepatic leukemia factor ( HLF ) chimeric proteins that contain the DNA-binding and protein dimerization domains of the basic leucine zipper ( bZIP ) protein HLF fused to a portion of E2A proteins with transcriptional activation properties .

The <dna>t ( 17 ; 19 )</dna> translocation in acute lymphoblastic leukemias results in creation of <protein>E2A-hepatic leukemia factor</protein> ( <protein>HLF</protein> ) <protein>chimeric proteins</protein> that contain the <protein>DNA-binding and protein dimerization domains</protein> of the <protein>basic leucine zipper ( bZIP ) protein</protein> <protein>HLF</protein> fused to a portion of <protein>E2A proteins</protein> with transcriptional activation properties .


An in vitro binding site selection procedure was used to determine DNA sequences preferentially bound by wild-type HLF and chimeric E2A-HLF proteins isolated from various t ( 17 ; 19 ) -bearing leukemias .

An in vitro binding site selection procedure was used to determine DNA sequences preferentially bound by <protein>wild-type HLF</protein> and <protein>chimeric E2A-HLF</protein> proteins isolated from various <cell_line>t ( 17 ; 19 ) -bearing leukemias</cell_line> .


All were found to selectively bind the consensus sequence 5'-GTTACGTAAT-3 ' with high affinity .

All were found to selectively bind the <dna>consensus sequence</dna> 5'-GTTACGTAAT-3 ' with high affinity .


Wild-type and chimeric HLF proteins also bound closely related sites identified previously for bZIP proteins of both the proline -and acidic amino acid-rich ( PAR ) and C/EBP subfamilies ; however , E2A-HLF proteins were significantly less tolerant of certain deviations from the HLF consensus binding site .

Wild-type and <protein>chimeric HLF proteins</protein> also bound closely related sites identified previously for <protein>bZIP proteins</protein> of both the <protein>proline</protein> -and acidic amino acid-rich ( <protein>PAR</protein> ) and <protein>C/EBP subfamilies</protein> ; however , <protein>E2A-HLF</protein> proteins were significantly less tolerant of certain deviations from the <dna>HLF consensus binding site</dna> .


These differences were directly attributable to loss of an HLF ancillary DNA-binding domain in all E2A-HLF chimeras and were further exacerbated by a zipper mutation in one isolate .

These differences were directly attributable to loss of an <dna>HLF ancillary DNA-binding domain</dna> in all <protein>E2A-HLF chimeras</protein> and were further exacerbated by a zipper mutation in one isolate .


Both wild-type and chimeric HLF proteins displayed transcriptional activator properties in lymphoid and nonlymphoid cells on reporter genes containing HLF or C/EBP consensus binding sites .

Both <protein>wild-type</protein> and <protein>chimeric HLF proteins</protein> displayed <protein>transcriptional activator</protein> properties in <cell_type>lymphoid and nonlymphoid cells</cell_type> on <dna>reporter genes</dna> containing <dna>HLF or C/EBP consensus binding sites</dna> .


But on reporter genes with nonoptimal binding sites , their transcriptional properties diverged and E2A-HLF competitively inhibited activation by wild-type PAR proteins .

But on <dna>reporter genes</dna> with <dna>nonoptimal binding sites</dna> , their transcriptional properties diverged and <protein>E2A-HLF</protein> competitively inhibited activation by <protein>wild-type PAR proteins</protein> .


These findings establish a spectrum of binding site-specific transcriptional properties for E2A-HLF which may preferentially activate expression of select subordinate genes as a homodimer and potentially antagonize expression of others through heteromeric interactions .

These findings establish a spectrum of binding site-specific transcriptional properties for <protein>E2A-HLF</protein> which may preferentially activate expression of select subordinate genes as a homodimer and potentially antagonize expression of others through heteromeric interactions .


ZAP-70 tyrosine kinase , CD45 , and T cell receptor involvement in UV- and H2O2-induced T cell signal transduction .

<protein>ZAP-70 tyrosine kinase</protein> , <protein>CD45</protein> , and <protein>T cell receptor</protein> involvement in UV- and H2O2-induced T cell signal transduction .


Several mammalian responses to UV irradiation , including the activation of NF-kappa B , are believed to involve tyrosine phosphorylation .

Several mammalian responses to UV irradiation , including the activation of <protein>NF-kappa B</protein> , are believed to involve tyrosine phosphorylation .


UV irradiation and H2O2 treatment of T lymphocytes induce protein tyrosine phosphorylation and Ca2+ signals similar to those observed following biological stimulation .

UV irradiation and H2O2 treatment of <cell_type>T lymphocytes</cell_type> induce protein tyrosine phosphorylation and Ca2+ signals similar to those observed following biological stimulation .


We have examined the role of cell surface molecules in these responses .


Normal T lymphocytes whose surface expression of CD3 was depleted showed impaired UV-induced tyrosine phosphorylation and Ca2+ signals .

Normal <cell_type>T lymphocytes</cell_type> whose surface expression of <protein>CD3</protein> was depleted showed impaired UV-induced tyrosine phosphorylation and Ca2+ signals .


Similarly , Jurkat T cell lines deficient in CD3 or CD45 expression also gave impaired UV responses .

Similarly , <cell_line>Jurkat T cell lines</cell_line> deficient in CD3 or CD45 expression also gave impaired UV responses .


However , all these cell types still gave strong Ca2+ and tyrosine phosphorylation responses to H2O2 .


The T cell tyrosine kinase ZAP-70 was found to be highly responsive to UV and H2O2 treatment .

The T cell tyrosine <protein>kinase ZAP-70</protein> was found to be highly responsive to UV and H2O2 treatment .


ZAP-70 responsiveness to UV required expression of both CD3 and CD45 , whereas only CD3 was required for the response to H2O2 .

<protein>ZAP-70</protein> responsiveness to UV required expression of both <protein>CD3</protein> and <protein>CD45</protein> , whereas only <protein>CD3</protein> was required for the response to H2O2 .


UV-induced activation of NF-kappa B was blocked by CD3 depletion , indicating the importance of such cell surface molecules in biological responses to UV .

UV-induced activation of <protein>NF-kappa B</protein> was blocked by <protein>CD3</protein> depletion , indicating the importance of such <protein>cell surface molecules</protein> in biological responses to UV .


In nonlymphoid cells , the epidermal growth factor receptor displayed increased tyrosine phosphorylation within seconds of UV irradiation .

In <cell_type>nonlymphoid cells</cell_type> , the <protein>epidermal growth factor receptor</protein> displayed increased tyrosine phosphorylation within seconds of UV irradiation .


These results suggest that UV-induced signal transduction is mediated via cell surface receptors that normally respond to biological stimulation , whereas H2O2 is able to partially bypass this requirement .

These results suggest that UV-induced signal transduction is mediated via <protein>cell surface receptors</protein> that normally respond to biological stimulation , whereas H2O2 is able to partially bypass this requirement .


Inhibition of the differentiation of human myeloid cell lines by redox changes induced through glutathione depletion .

Inhibition of the differentiation of <cell_line>human myeloid cell lines</cell_line> by redox changes induced through glutathione depletion .


We have investigated the effect of redox changes in vivo on the differentiation of two human myeloid cell lines , HL-60 and KG-1 .

We have investigated the effect of redox changes in vivo on the differentiation of two <cell_line>human myeloid cell lines</cell_line> , <cell_line>HL-60</cell_line> and <cell_line>KG-1</cell_line> .


The glutathione-depleting agent diethyl maleate ( DEM ) prevented the development of differentiated features in response to phorbol esters , including adherence of the cells to plastic surfaces and repression of the myeloperoxidase and CD34 genes .

The glutathione-depleting agent diethyl maleate ( DEM ) prevented the development of differentiated features in response to phorbol esters , including adherence of the cells to plastic surfaces and repression of the <dna>myeloperoxidase and CD34 genes</dna> .


Moreover , DEM abolished phorbol 12-myristate 13-acetate-induced activation of the transcription factors AP-1 and Egr-1 , suggesting that inhibition of differentiation may be due , at least in part , to redox modifications of these proteins .

Moreover , DEM abolished phorbol 12-myristate 13-acetate-induced activation of the <protein>transcription factors</protein> <protein>AP-1</protein> and <protein>Egr-1</protein> , suggesting that inhibition of differentiation may be due , at least in part , to redox modifications of these <protein>proteins</protein> .


Lipopolysaccharide induction of tissue factor gene expression in monocytic cells is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site .

Lipopolysaccharide induction of <dna>tissue factor gene</dna> expression in <cell_type>monocytic cells</cell_type> is mediated by binding of <protein>c-Rel/p65 heterodimers</protein> to a <dna>kappa B-like site</dna> .


Exposure of monocytic cells to bacterial lipopolysaccharide ( LPS ) activates the NF-kappa B/Rel family of proteins and leads to the rapid induction of inflammatory gene products , including tissue factor ( TF ) .

Exposure of <cell_type>monocytic cells</cell_type> to bacterial lipopolysaccharide ( LPS ) activates the <protein>NF-kappa B/Rel family</protein> of proteins and leads to the rapid induction of <protein>inflammatory gene products</protein> , including <protein>tissue factor</protein> ( <protein>TF</protein> ) .


TF is the primary cellular initiator of the coagulation protease cascades .

<protein>TF</protein> is the primary cellular initiator of the <protein>coagulation protease</protein> cascades .


Here we report the characterization of a nuclear complex from human monocytic cells that bound to a kappa B-like site , 5'-CGGAGTTTCC-3 ' , in the 5'-flanking region of the human TF gene .

Here we report the characterization of a <protein>nuclear complex</protein> from human <cell_type>monocytic cells</cell_type> that bound to a <dna>kappa B-like site</dna> , <dna>5'-CGGAGTTTCC-3 '</dna> , in the <dna>5'-flanking region</dna> of the <dna>human TF gene</dna> .


This nuclear complex was activated by LPS with kinetics that preceded induction of the TF gene .

This <protein>nuclear complex</protein> was activated by LPS with kinetics that preceded induction of the <dna>TF gene</dna> .


In vitro binding studies demonstrated that the TF site bound translated c-Rel and p65 homodimers but not p50/p65 heterodimers or p50 homodimers .

In vitro binding studies demonstrated that the <dna>TF site</dna> bound translated <protein>c-Rel and p65 homodimers</protein> but not <protein>p50/p65 heterodimers</protein> or <protein>p50 homodimers</protein> .


Base-pair substitutions in the TF site indicated that the presence of a cytosine at position 1 precluded binding of NF-kappa B .

Base-pair substitutions in the <dna>TF site</dna> indicated that the presence of a cytosine at <protein>position 1</protein> precluded binding of <protein>NF-kappa B</protein> .


In fact , under low-ionic-strength conditions , the TF complex did not migrate with translated p50/p65 dimers but instead comigrated with c-Rel/p65 dimers .

In fact , under low-ionic-strength conditions , the <protein>TF complex</protein> did not migrate with translated <protein>p50/p65 dimers</protein> but instead comigrated with <protein>c-Rel/p65 dimers</protein> .


Antibodies against the NF-kappa B and Rel proteins and UV cross-linking studies revealed the presence of c-Rel and p65 and the absence of p50 in the TF complex and further showed that c-Rel/p65 heterodimers selectively bound to the TF kappa B-like site .

Antibodies against the <protein>NF-kappa B</protein> and Rel proteins and UV cross-linking studies revealed the presence of <protein>c-Rel</protein> and p65 and the absence of <protein>p50</protein> in the <protein>TF complex</protein> and further showed that <protein>c-Rel/p65 heterodimers</protein> selectively bound to the <dna>TF kappa B-like site</dna> .


Functional studies indicated that the TF site conferred LPS inducibility on a heterologous promoter and was transactivated by c-Rel or p65 .

Functional studies indicated that the <dna>TF site</dna> conferred LPS inducibility on a <dna>heterologous promoter</dna> and was transactivated by <protein>c-Rel</protein> or p65 .


Taken together , our results demonstrated that binding of c-Rel/p65 heterodimers to a novel kappa B-like site mediated LPS induction of TF gene expression in monocytic cells .

Taken together , our results demonstrated that binding of <protein>c-Rel/p65 heterodimers</protein> to a novel <dna>kappa B-like site</dna> mediated LPS induction of <protein>TF</protein> gene expression in <cell_type>monocytic cells</cell_type> .


Inhibition of T cell activation by the extracellular matrix protein tenascin .

Inhibition of T cell activation by the <protein>extracellular matrix protein</protein> <protein>tenascin</protein> .


Tenascin ( TN ) is an extracellular matrix protein that is expressed widely in the fetus and sparingly in the adult , but reappears at high levels in certain areas of tissue insult such as tumor matrices and sites of wound healing .

<protein>Tenascin</protein> ( <protein>TN</protein> ) is an <protein>extracellular matrix protein</protein> that is expressed widely in the fetus and sparingly in the adult , but reappears at high levels in certain areas of tissue insult such as tumor matrices and sites of wound healing .


We show here that soluble TN inhibits proliferation of human T cells in response to alpha CD3 Ab co-immobilized with the extracellular matrix protein fibronectin ( FN ) .

We show here that soluble <protein>TN</protein> inhibits proliferation of <cell_type>human T cells</cell_type> in response to <protein>alpha CD3 Ab</protein> co-immobilized with the <protein>extracellular matrix protein</protein> <protein>fibronectin</protein> ( <protein>FN</protein> ) .


TN also inhibits proliferation driven by alpha CD3/IL-2 or by phorbol ester/IL-2 , and it prevents high level induction of IL-2R .

<protein>TN</protein> also inhibits proliferation driven by <protein>alpha CD3/IL-2</protein> or by <protein>phorbol ester/IL-2 ,</protein> and it prevents high level induction of <protein>IL-2R</protein> .


The presence of TN in culture medium does not detectably alter the pattern of tyrosine phosphorylation resulting from T cell triggering with alpha CD3 , but at later time points prevents the appearance of functional NF-AT1 transcription factor complexes in T cell nuclear extracts .

The presence of <protein>TN</protein> in culture medium does not detectably alter the pattern of tyrosine phosphorylation resulting from T cell triggering with <protein>alpha CD3</protein> , but at later time points prevents the appearance of functional <protein>NF-AT1 transcription factor complexes</protein> in T cell nuclear extracts .


These findings are consistent with the postulated role for TN as a natural antagonist to FN action , and suggest that T cell responses occurring at tissue sites in which TN is expressed could be influenced by its presence .

These findings are consistent with the postulated role for <protein>TN</protein> as a natural antagonist to <protein>FN</protein> action , and suggest that T cell responses occurring at tissue sites in which <protein>TN</protein> is expressed could be influenced by its presence .


Human immunodeficiency virus type 1 Nef protein down-regulates transcription factors NF-kappa B and AP-1 in human T cells in vitro after T-cell receptor stimulation .

Human immunodeficiency virus type 1 Nef protein down-regulates <protein>transcription factors</protein> <protein>NF-kappa B</protein> and <protein>AP-1</protein> in <cell_type>human T cells</cell_type> in vitro after T-cell receptor stimulation .


Human immunodeficiency virus type 1 ( HIV-1 ) negative factor ( Nef ) has been shown to down-regulate the transcription factors NF-kappa B and AP-1 in vitro .

Human immunodeficiency virus type 1 ( HIV-1 ) <protein>negative factor</protein> ( <protein>Nef</protein> ) has been shown to down-regulate the <protein>transcription factors</protein> <protein>NF-kappa B</protein> and <protein>AP-1</protein> in vitro .


To define the mechanism of action of the Nef protein , the signal transduction pathways which may be affected in T cells by constitutive expression of the nef gene were examined .

To define the mechanism of action of the <protein>Nef</protein> protein , the signal transduction pathways which may be affected in <cell_type>T cells</cell_type> by constitutive expression of the nef gene were examined .


Stimulation of T cells with tumor necrosis factor , interleukin-1 , or lipopolysaccharide resulted in the recruitment of transcriptional factors to a similar level whether or not the cells expressed the nef gene .

Stimulation of <cell_type>T cells</cell_type> with tumor necrosis factor , interleukin-1 , or lipopolysaccharide resulted in the recruitment of transcriptional factors to a similar level whether or not the cells expressed the nef gene .


On the other hand , stimulation of T cells by mitogens or antibodies to the T-cell receptor ( TCR ) - CD3 complex resulted in the down-regulation of transcriptional factors NF-kappa B and AP-1 in cells expressing the nef gene compared with cells not expressing the nef gene .

On the other hand , stimulation of <cell_type>T cells</cell_type> by mitogens or antibodies to the T-cell receptor ( TCR ) - <protein>CD3</protein> complex resulted in the down-regulation of transcriptional factors <protein>NF-kappa B</protein> and <protein>AP-1</protein> in cells expressing the nef gene compared with cells not expressing the nef gene .


Because the Nef protein does not affect the surface expression of the CD3 -TCR complex , we conclude that the Nef protein down-regulates the transcriptional factors NF-kappa B and AP-1 in T cells in vitro through an effect on the TCR-dependent signal transduction pathway .

Because the <protein>Nef</protein> protein does not affect the surface expression of the <protein>CD3</protein> -TCR complex , we conclude that the <protein>Nef</protein> protein down-regulates the transcriptional factors <protein>NF-kappa B</protein> and <protein>AP-1</protein> in <cell_type>T cells</cell_type> in vitro through an effect on the TCR-dependent signal transduction pathway .


Effects of alpha-lipoic acid and dihydrolipoic acid on expression of proto-oncogene c-fos .

Effects of alpha-lipoic acid and dihydrolipoic acid on expression of <dna>proto-oncogene c-fos</dna> .


The transcription factor AP-1 is an important human mediator of the cellular response to serum , growth factors , and phorbol esters such as 12-O-tetradecanoyl-phorbol-13 acetate ( TPA ) .

The <protein>transcription factor</protein> <protein>AP-1</protein> is an important human mediator of the cellular response to serum , <protein>growth factors</protein> , and phorbol esters such as 12-O-tetradecanoyl-phorbol-13 acetate ( TPA ) .


The AP-1 complex consists of distinct protein heterodimers encoded by the proto-oncogene c-fos and c-jun mRNA whose gene expression can be induced by TPA , cyclic AMP and growth factors .

The <protein>AP-1</protein> complex consists of distinct <protein>protein heterodimers</protein> encoded by the <dna>proto-oncogene c-fos</dna> and <rna>c-jun mRNA</rna> whose gene expression can be induced by TPA , cyclic AMP and <protein>growth factors</protein> .


Recent findings suggest an involvement of reactive oxygen species in the pathway of TPA and protein kinase C leading to expression of c-fos and c-jun mRNA .

Recent findings suggest an involvement of reactive oxygen species in the pathway of TPA and <protein>protein kinase C</protein> leading to expression of <rna>c-fos and c-jun mRNA</rna> .


To investigate the role of reactive oxygen species we studied the effects of alpha-lipoic acid and dihydrolipoic acid ( natural thiol antioxidants ) on the expression of c-fos mRNA in human Jurkat T cells .

To investigate the role of reactive oxygen species we studied the effects of alpha-lipoic acid and dihydrolipoic acid ( natural thiol antioxidants ) on the expression of <rna>c-fos mRNA</rna> in <cell_line>human Jurkat T cells</cell_line> .


When cells were preincubated with dihydrolipoic acid ( 0.2 mM ) the expression of c-fos mRNA was suppressed at 30 min after stimulation of TPA ( 0.5 microM ) whereas in the case of preincubation of alpha-lipoic acid ( 0.2 microM ) , the expression was enhanced at 30 min .

When cells were preincubated with dihydrolipoic acid ( 0.2 mM ) the expression of <rna>c-fos mRNA</rna> was suppressed at 30 min after stimulation of TPA ( 0.5 microM ) whereas in the case of preincubation of alpha-lipoic acid ( 0.2 microM ) , the expression was enhanced at 30 min .


These studies support the idea that superoxide anion radical plays a role in the expression of c-fos mRNA .

These studies support the idea that superoxide anion radical plays a role in the expression of <rna>c-fos mRNA</rna> .


Appraisal of potential therapeutic index of antioxidants on the basis of their in vitro effects on HIV replication in monocytes and interleukin 2 -induced lymphocyte proliferation .

Appraisal of potential therapeutic index of antioxidants on the basis of their in vitro effects on HIV replication in <cell_type>monocytes</cell_type> and <protein>interleukin 2</protein> -induced lymphocyte proliferation .


Antioxidant molecules have been suggested to be of therapeutic value in the treatment of HIV-infected patients .


To evaluate this possibility , we examined in vitro the effects of two types of antioxidant molecules in terms of inhibition of HIV replication in monocytes , one of the main reservoirs of HIV , and also in terms of modulation of the immune competence as measured by PBMC proliferation .

To evaluate this possibility , we examined in vitro the effects of two types of antioxidant molecules in terms of inhibition of HIV replication in <cell_type>monocytes</cell_type> , one of the main reservoirs of HIV , and also in terms of modulation of the immune competence as measured by <cell_type>PBMC</cell_type> proliferation .


We tested the effects of BHA , a phenolic , lipid-soluble , chain-breaking antioxidant , and NAC , a known glutathione precursor with some direct free-radical scavenging properties as well , on the regulation of HIV-1 expression in latently infected U1 cells and in productively and chronically infected U937 cells .

We tested the effects of BHA , a phenolic , lipid-soluble , chain-breaking antioxidant , and NAC , a known glutathione precursor with some direct free-radical scavenging properties as well , on the regulation of HIV-1 expression in latently infected <cell_line>U1 cells</cell_line> and in productively and chronically infected <cell_line>U937 cells</cell_line> .


Both antioxidants inhibited TNF -or PMA-induced NF-kappa B activity in U1 cells , as well as the sustained NF-kappa B activity permanently induced by the virus itself in chronically HIV-infected U937 cells .

Both antioxidants inhibited <protein>TNF</protein> -or PMA-induced <protein>NF-kappa B</protein> activity in <cell_line>U1 cells</cell_line> , as well as the sustained <protein>NF-kappa B</protein> activity permanently induced by the virus itself in chronically HIV-infected <cell_line>U937 cells</cell_line> .


This resulted in only a partial inhibition of TNF -or PMA- induced HIV replication in U1 cells , and no detectable effect on HIV replication in chronically infected U937 cells .

This resulted in only a partial inhibition of <protein>TNF</protein> -or PMA- induced HIV replication in <cell_line>U1 cells</cell_line> , and no detectable effect on HIV replication in <cell_line>chronically infected U937 cells</cell_line> .


This may be the first limitation to potential antiviral effects of antioxidant therapies .


Another limitation is that antioxidant concentrations high enough to block NK-kappa B activation were shown to have a suppressive effect on immune functions in vitro , because NAC and BHA blocked IL-2-induced PBMC proliferation .

Another limitation is that antioxidant concentrations high enough to block <protein>NK-kappa B</protein> activation were shown to have a suppressive effect on immune functions in vitro , because NAC and BHA blocked <cell_type>IL-2-induced PBMC</cell_type> proliferation .


These data warrant prudence in the design of antioxidant-based therapies aimed at suppressing HIV replication .


Isolation and characterization of gelatinase granules from human neutrophils .

Isolation and characterization of gelatinase granules from <cell_type>human neutrophils</cell_type> .


We recently confirmed the existence of gelatinase granules as a subpopulation of peroxidase-negative granules by double-labeling immunogold electron microscopy on intact cells and by subcellular fractionation .


Further characterization of gelatinase granules has been hampered by poor separation of specific and gelatinase granules on both two-layer Percoll gradients and sucrose gradients .


We have developed a three-layer Percoll density gradient that allows separation of the different granules and vesicles from human neutrophils ; in particular , it allows separation of specific and gelatinase granules .

We have developed a three-layer Percoll density gradient that allows separation of the different granules and vesicles from <cell_type>human neutrophils</cell_type> ; in particular , it allows separation of specific and gelatinase granules .


This allows us to characterize these two granule populations with regard to their content of membrane proteins , which become incorporated into the plasma membrane during exocytosis .

This allows us to characterize these two granule populations with regard to their content of <protein>membrane proteins</protein> , which become incorporated into the plasma membrane during exocytosis .


We found that gelatinase granules , defined as peroxidase-negative granules containing gelatinase but lacking lactoferrin , contain 50 % of total cell gelatinase , with the remaining residing in specific granules .

We found that gelatinase granules , defined as peroxidase-negative granules containing <protein>gelatinase</protein> but lacking <protein>lactoferrin</protein> , contain 50 % of total cell <protein>gelatinase</protein> , with the remaining residing in specific granules .


Furthermore , we found that 20 % to 25 % of both the adhesion protein Mac-1 and the NADPH-oxidase component cytochrome b558 is localized in gelatinase granules .

Furthermore , we found that 20 % to 25 % of both the <protein>adhesion protein Mac-1</protein> and the <protein>NADPH-oxidase component cytochrome</protein> <protein>b558</protein> is localized in <protein>gelatinase</protein> granules .


Although no qualitative difference was observed between specific granules and gelatinase granules with respect to cytochrome b558 and Mac-1 , stimulation of the neutrophil with FMLP resulted in a selective mobilization of the least dense peroxidase-negative granules , ie , gelatinase granules , which , in concert with secretory vesicles , furnish the plasma membrane with Mac-1 and cytochrome b558 .

Although no qualitative difference was observed between specific granules and <protein>gelatinase</protein> granules with respect to <protein>cytochrome b558</protein> and <protein>Mac-1</protein> , stimulation of the <cell_type>neutrophil</cell_type> with <protein>FMLP</protein> resulted in a selective mobilization of the least dense peroxidase-negative granules , ie , <protein>gelatinase</protein> granules , which , in concert with secretory vesicles , furnish the plasma membrane with <protein>Mac-1</protein> and <protein>cytochrome b558</protein> .


This shows that gelatinase granules are functionally important relative to specific granules in mediating early inflammatory responses .

This shows that <protein>gelatinase</protein> granules are functionally important relative to specific granules in mediating early inflammatory responses .


Regulation of interleukin-2 receptor alpha chain expression and nuclear factor.kappa B activation by protein kinase C in T lymphocytes .

Regulation of <protein>interleukin-2 receptor alpha chain</protein> expression and <protein>nuclear factor.kappa B</protein> activation by <protein>protein kinase C</protein> in <cell_type>T lymphocytes</cell_type> .


Autocrine role of tumor necrosis factor alpha .

Autocrine role of <protein>tumor necrosis factor alpha</protein> .


The regulation of interleukin-2 receptor alpha chain ( IL-2R alpha ) expression and nuclear factor ( NF ) activation by protein kinase C ( PKC ) in resting T cells , has been studied .

The regulation of <protein>interleukin-2 receptor alpha chain</protein> ( <protein>IL-2R alpha</protein> ) expression and <protein>nuclear factor</protein> ( NF ) activation by <protein>protein kinase C</protein> ( <protein>PKC</protein> ) in <cell_type>resting T cells</cell_type> , has been studied .


Treatment of human resting T cells with phorbol esters strongly induced the expression of IL-2R alpha and the activation of NF.kappa B .

Treatment of human <cell_type>resting T cells</cell_type> with phorbol esters strongly induced the expression of <protein>IL-2R alpha</protein> and the activation of <protein>NF.kappa B</protein> .


This activation was due to the translocation of p65 and c-Rel NF.kappa B proteins from cytoplasmic stores to the nucleus , where they bound the kappa B sequence of the IL-2R alpha promoter either as p50.p65 or as p50.c-Rel heterodimers .

This activation was due to the translocation of <protein>p65</protein> and <protein>c-Rel</protein> <protein>NF.kappa B</protein> proteins from cytoplasmic stores to the nucleus , where they bound the <dna>kappa B sequence</dna> of the <dna>IL-2R alpha promoter</dna> either as <protein>p50.p65</protein> or as <protein>p50.c-Rel</protein> heterodimers .


Interestingly , all of those events were largely indirect and mediated by endogenously secreted tumor necrosis factor alpha ( TNF alpha ) , as they were strongly inhibited by a neutralizing anti-TNF alpha monoclonal antibody .

Interestingly , all of those events were largely indirect and mediated by endogenously secreted <protein>tumor necrosis factor alpha</protein> ( <protein>TNF alpha</protein> ) , as they were strongly inhibited by a <protein>neutralizing anti-TNF alpha monoclonal antibody</protein> .


Furthermore , cyclosporin A , which blocked TNF alpha production induced by PKC , strongly inhibited IL-2R alpha and NF.kappa B activation .

Furthermore , cyclosporin A , which blocked <protein>TNF alpha</protein> production induced by <protein>PKC</protein> , strongly inhibited <protein>IL-2R alpha</protein> and <protein>NF.kappa B</protein> activation .


The addition of either TNF alpha or IL-2 partially recovered cyclosporin A-induced IL-2R alpha inhibition , but only TNF alpha completely recovered NF.kappa B activation .

The addition of either <protein>TNF alpha</protein> or <protein>IL-2</protein> partially recovered cyclosporin A-induced <protein>IL-2R alpha</protein> inhibition , but only <protein>TNF alpha</protein> completely recovered <protein>NF.kappa B</protein> activation .


Those results indicate that , in resting T cells , PKC activation has only a triggering role , whereas the endogenously secreted TNF alpha plays an essential role in the quantitative control of the expression of IL-2R alpha chain or NF.kappa B activation .

Those results indicate that , in <cell_type>resting T cells</cell_type> , <protein>PKC</protein> activation has only a triggering role , whereas the endogenously secreted <protein>TNF alpha</protein> plays an essential role in the quantitative control of the expression of <protein>IL-2R alpha</protein> chain or <protein>NF.kappa B</protein> activation .


Superantigens activate HIV-1 gene expression in monocytic cells .

<protein>Superantigens</protein> activate HIV-1 gene expression in <cell_type>monocytic cells</cell_type> .


Binding of superantigens to MHC class II molecules results in transduction of biochemical signals leading to cellular activation and gene expression .

Binding of superantigens to <protein>MHC class II molecules</protein> results in transduction of biochemical signals leading to cellular activation and gene expression .


We demonstrate that the staphylococcal superantigens toxic shock syndrome toxin-1 ( TSST-1 ) and staphylococcal enterotoxin A ( SEA ) activate HIV-1-LTR -driven transcription of chloramphenicol acetyl transferase in the human monocytic cell line THP-1 .

We demonstrate that the <protein>staphylococcal superantigens</protein> <protein>toxic shock syndrome toxin-1</protein> ( <protein>TSST-1</protein> ) and <protein>staphylococcal enterotoxin A</protein> ( <protein>SEA</protein> ) activate <dna>HIV-1-LTR</dna> -driven transcription of <protein>chloramphenicol acetyl transferase</protein> in the <cell_line>human monocytic cell line</cell_line> <cell_line>THP-1</cell_line> .


Induction of HIV-1- LTR -driven transcription in THP-1 cells by superantigens was associated with the induction of nuclear factor-kappa B DNA-binding activity .

Induction of HIV-1- <dna>LTR</dna> -driven transcription in <cell_line>THP-1 cells</cell_line> by <protein>superantigens</protein> was associated with the induction of <protein>nuclear factor-kappa B</protein> DNA-binding activity .


Superantigens also increased viral protein secretion from the granulocyte-macrophage colony-stimulating factor-pretreated chronically infected human monocytic cell line U1 .

<protein>Superantigens</protein> also increased viral protein secretion from the <cell_line>granulocyte-macrophage colony-stimulating factor-pretreated chronically infected human monocytic cell line U1</cell_line> .


Induction of HIV-1 gene expression in monocytic cells by superantigens occurred via tumor necrosis factor-alpha-dependent and -independent mechanisms .

Induction of HIV-1 gene expression in <cell_type>monocytic cells</cell_type> by <protein>superantigens</protein> occurred via tumor necrosis factor-alpha-dependent and -independent mechanisms .


Our results suggest that superantigens and other MHC class II ligands may activate HIV-1 gene expression in monocytes/macrophages .

Our results suggest that <protein>superantigens</protein> and other <protein>MHC class II ligands</protein> may activate HIV-1 gene expression in <cell_type>monocytes/macrophages</cell_type> .


Mitogen activation of human peripheral T lymphocytes induces the formation of new cyclic AMP response element-binding protein nuclear complexes .

Mitogen activation of <cell_type>human peripheral T lymphocytes</cell_type> induces the formation of new <protein>cyclic AMP response element-binding protein nuclear complexes</protein> .


A large body of evidence indicates that experimental agents which raise cellular cAMP levels inhibit T cell growth and division .


By contrast , many studies have reported that mitogen activation of T cells increases cAMP levels , implying a positive physiological role for cAMP in the activation process .

By contrast , many studies have reported that <protein>mitogen</protein> activation of <cell_type>T cells</cell_type> increases cAMP levels , implying a positive physiological role for cAMP in the activation process .


In the present study we demonstrate that mitogen activation of human peripheral T lymphocytes induces nuclear factors that form complexes with cyclic AMP response element-binding protein ( CREB ) .

In the present study we demonstrate that <protein>mitogen</protein> activation of <cell_type>human peripheral T lymphocytes</cell_type> induces nuclear factors that form complexes with <protein>cyclic AMP response element-binding protein</protein> ( <protein>CREB</protein> ) .


Four complexes are identified by the electrophoretic mobility shift assay , two of which are induced by mitogen activation .

Four complexes are identified by the electrophoretic mobility shift assay , two of which are induced by <protein>mitogen</protein> activation .


All four complexes contain CREB and are bound to the cAMP response element ( CRE ) core sequence ( TGACGTCA ) , as indicated by antibody and oligonucleotide competition experiments .

All four complexes contain <protein>CREB</protein> and are bound to the <dna>cAMP response element ( CRE ) core sequence</dna> ( TGACGTCA ) , as indicated by antibody and oligonucleotide competition experiments .


Binding of the four complexes to CRE is prevented by dephosphorylation of nuclear extracts and is restored by rephosphorylation with cAMP-dependent protein kinase or endogenous kinases .

Binding of the four complexes to <dna>CRE</dna> is prevented by dephosphorylation of nuclear extracts and is restored by rephosphorylation with <protein>cAMP-dependent protein kinase</protein> or <protein>endogenous kinases</protein> .


Similar complexes are detected in nuclear extracts of Jurkat cells .

Similar complexes are detected in nuclear extracts of <cell_line>Jurkat cells</cell_line> .


Mitogen induction of the electrophoretic mobility shift assay complexes is not accounted for by protein phosphorylation or by induction of CREB .

Mitogen induction of the <protein>electrophoretic mobility shift assay complexes</protein> is not accounted for by protein phosphorylation or by induction of <protein>CREB</protein> .


Rather , the data indicate that mitogen increases the levels of a nuclear factor ( s ) that dimerizes with CREB .

Rather , the data indicate that mitogen increases the levels of a nuclear factor ( s ) that dimerizes with <protein>CREB</protein> .


Induction of new CREB complexes implies a physiological role for cAMP in mitogen activation of T lymphocytes .

Induction of new <protein>CREB complexes</protein> implies a physiological role for cAMP in <protein>mitogen</protein> activation of <cell_type>T lymphocytes</cell_type> .


Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells .

Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to <cell_line>cultured human endothelial cells</cell_line> .


Antioxidants have been proposed to be anti-atherosclerotic agents ; however , the mechanisms underlying their beneficial effects are poorly understood .


We have examined the effect of alpha-tocopherol ( alpha-tcp ) on one cellular event in atherosclerotic plaque development , monocyte adhesion to stimulated endothelial cells ( ECs ) .

We have examined the effect of alpha-tocopherol ( alpha-tcp ) on one cellular event in atherosclerotic plaque development , monocyte adhesion to <cell_type>stimulated endothelial cells</cell_type> ( <cell_type>ECs</cell_type> ) .


Human umbilical vein ECs were pretreated with alpha-tcp before stimulation with known agonists of monocyte adhesion : IL-1 ( 10 ng/ml ) , LPS ( 10 ng/ml ) , thrombin ( 30 U/ml ) , or PMA ( 10 nM ) .

Human umbilical vein <cell_type>ECs</cell_type> were pretreated with alpha-tcp before stimulation with known agonists of monocyte adhesion : <protein>IL-1</protein> ( 10 ng/ml ) , LPS ( 10 ng/ml ) , <protein>thrombin</protein> ( 30 U/ml ) , or PMA ( 10 nM ) .


Agonist-induced monocytic cell adhesion , but not basal adhesion , was inhibited in a time- and concentration-dependent manner by alpha-tcp .


The IC50 of alpha-tcp on an IL-1 -induced response was 45 microM .

The IC50 of alpha-tcp on an <protein>IL-1</protein> -induced response was 45 microM .


The inhibition correlated with a decrease in steady state levels of E-selectin mRNA and cell surface expression of E-selectin which is consistent with the ability of a monoclonal antibody to E-selectin to inhibit monocytic cell adhesion in this system .

The inhibition correlated with a decrease in steady state levels of <rna>E-selectin mRNA</rna> and cell surface expression of <protein>E-selectin</protein> which is consistent with the ability of a <protein>monoclonal antibody</protein> to <protein>E-selectin</protein> to inhibit monocytic cell adhesion in this system .


Probucol ( 50 microM ) and N-acetylcysteine ( 20 mM ) also inhibited agonist-induced monocytic cell adhesion ; whereas , several other antioxidants had no significant effect .


Protein kinase C ( PKC ) does not appear to play a role in the alpha-tcp effect since no suppression of phosphorylation of PKC substrates was observed .

<protein>Protein kinase C</protein> ( <protein>PKC</protein> ) does not appear to play a role in the alpha-tcp effect since no suppression of phosphorylation of <protein>PKC</protein> substrates was observed .


Activation of the transcription factor NF-kappa B is reported to be necessary but not sufficient for E-selectin expression in EC .

Activation of the <protein>transcription factor</protein> <protein>NF-kappa B</protein> is reported to be necessary but not sufficient for <protein>E-selectin</protein> expression in <cell_line>EC</cell_line> .


Electrophoretic mobility shift assays failed to show an alpha-tcp-induced decrease in activation of this transcription factor after cytokine stimulation .

Electrophoretic mobility shift assays failed to show an alpha-tcp-induced decrease in activation of this <protein>transcription factor</protein> after <protein>cytokine</protein> stimulation .


It has been hypothesized that alpha-tcp acts as an anti-atherosclerotic molecule by inhibiting generation of oxidized LDL -- a putative triggering molecule in the atherosclerotic process .


Our results point to a novel alternative mechanism of action of alpha-tcp .


Central nervous system-derived cells express a kappa B-binding activity that enhances human immunodeficiency virus type 1 transcription in vitro and facilitates TAR -independent transactivation by Tat .

<cell_type>Central nervous system-derived cells</cell_type> express a kappa B-binding activity that enhances human immunodeficiency virus type 1 transcription in vitro and facilitates <dna>TAR</dna> -independent transactivation by <protein>Tat</protein> .


The Tat protein of human immunodeficiency virus type 1 ( HIV-1 ) is a potent activator of long terminal repeat -directed transcription .

The <protein>Tat protein</protein> of human immunodeficiency virus type 1 ( HIV-1 ) is a potent activator of <dna>long terminal repeat</dna> -directed transcription .


While in most cell types , activation requires interaction of Tat with the unusual transcription element TAR , astrocytic glial cells support TAR -independent transactivation of HIV-1 transcription by Tat .

While in most cell types , activation requires interaction of Tat with the unusual <dna>transcription element</dna> <dna>TAR</dna> , <cell_type>astrocytic glial cells</cell_type> support <dna>TAR</dna> -independent transactivation of HIV-1 transcription by Tat .


This alternative pathway of Tat activation is mediated by the viral enhancer , a kappa B domain capable of binding the prototypical form of the transcription factor nuclear factor kappa B ( NF-kappa B ) present in many cell types , including T lymphocytes .

This alternative pathway of <protein>Tat</protein> activation is mediated by the <dna>viral enhancer</dna> , a kappa B domain capable of binding the prototypical form of the <protein>transcription factor</protein> nuclear factor kappa B ( <protein>NF-kappa B</protein> ) present in many cell types , including <cell_type>T lymphocytes</cell_type> .


Tat transactivation mediated by the kappa B domain is sufficient to allow replication of TAR -deleted mutant HIV-1 in astrocytes .

<protein>Tat</protein> transactivation mediated by the <dna>kappa B domain</dna> is sufficient to allow replication of <dna>TAR</dna> -deleted mutant HIV-1 in <cell_type>astrocytes</cell_type> .


The present study demonstrates the existence of kappa B-specific binding factors present in human glial astrocytes that differ from prototypical NF-kappa B .

The present study demonstrates the existence of <protein>kappa B-specific binding factors</protein> present in <cell_type>human glial astrocytes</cell_type> that differ from prototypical <protein>NF-kappa B</protein> .


The novel astrocyte-derived kappa B-binding activity is retained on an HIV-1 Tat affinity column , while prototypical NF-kappa B from Jurkat T cells is not .

The novel astrocyte-derived kappa B-binding activity is retained on an HIV-1 <protein>Tat</protein> affinity column , while prototypical <protein>NF-kappa B</protein> from <cell_line>Jurkat T cells</cell_line> is not .


In vitro transcription studies demonstrate that astrocyte-derived kappa B-binding factors activate transcription of the HIV-1 long terminal repeat and that this activation is dependent on the kappa B domain .

In vitro transcription studies demonstrate that <protein>astrocyte-derived kappa B-binding factors</protein> activate transcription of the <dna>HIV-1 long terminal repeat</dna> and that this activation is dependent on the <dna>kappa B domain</dna> .


Moreover , TAR -independent transactivation of HIV-1 transcription is reproduced in vitro in an astrocyte factor-dependent manner which correlates with kappa B-binding activity .

Moreover , <dna>TAR</dna> -independent transactivation of HIV-1 transcription is reproduced in vitro in an astrocyte factor-dependent manner which correlates with kappa B-binding activity .


The importance of the central nervous system-enriched kappa B transcription factor in the regulation of HIV-1 expression is discussed .

The importance of the <protein>central nervous system-enriched kappa B</protein> <protein>transcription factor</protein> in the regulation of HIV-1 expression is discussed .


Human interleukin-13 activates the interleukin-4-dependent transcription factor NF-IL4 sharing a DNA binding motif with an interferon-gamma-induced nuclear binding factor .

<protein>Human interleukin-13</protein> activates the <protein>interleukin-4-dependent transcription factor</protein> <protein>NF-IL4</protein> sharing a <protein>DNA binding motif</protein> with an <protein>interferon-gamma-induced nuclear binding factor</protein> .


The effects of interleukin-13 ( IL-13 ) and interleukin-4 ( IL-4 ) on cellular functions were shown to be quite similar .

The effects of <protein>interleukin-13</protein> ( <protein>IL-13</protein> ) and <protein>interleukin-4</protein> ( <protein>IL-4</protein> ) on cellular functions were shown to be quite similar .


We provide evidence that in monocytes as well as in T lymphocytes both IL-4 and IL-13 activate the same recently identified transcription factor NF-IL4 which binds to the specific responsive element IL-4RE .

We provide evidence that in monocytes as well as in <cell_type>T lymphocytes</cell_type> both <protein>IL-4</protein> and <protein>IL-13</protein> activate the same recently identified <protein>transcription factor</protein> <protein>NF-IL4</protein> which binds to the <dna>specific responsive element IL-4RE</dna> .


In addition , we show that a nuclear factor activated by interferon-gamma also interacts with the IL-4RE .

In addition , we show that a <protein>nuclear factor</protein> activated by interferon-gamma also interacts with the <dna>IL-4RE</dna> .


It differs from NF-IL4 in the electrophoretic mobility of the complex with DNA , in its DNA-binding specificity and in the proteins interacting with the DNA sequence .

It differs from <protein>NF-IL4</protein> in the electrophoretic mobility of the complex with DNA , in its DNA-binding specificity and in the proteins interacting with the <dna>DNA sequence</dna> .


Sensitivity against various enzyme inhibitors suggests that components of the signal transduction pathway are shared by all three cytokines .

Sensitivity against various enzyme inhibitors suggests that components of the signal transduction pathway are shared by all three <protein>cytokines</protein> .


Encephalomyocarditis virus internal ribosomal entry site RNA-protein interactions .


Translational initiation of encephalomyocarditis virus ( EMCV ) mRNA occurs by ribosomal entry into the 5 ' nontranslated region of the EMCV mRNA , rather than by ribosomal scanning .

Translational initiation of <rna>encephalomyocarditis virus ( EMCV ) mRNA</rna> occurs by ribosomal entry into the <dna>5 ' nontranslated region</dna> of the <rna>EMCV mRNA</rna> , rather than by ribosomal scanning .


Internal ribosomal binding requires a cis-acting element termed the internal ribosomal entry site ( IRES ) .

Internal ribosomal binding requires a <dna>cis-acting element</dna> termed the <dna>internal ribosomal entry site</dna> ( <dna>IRES</dna> ) .


IRES elements have been proposed to be involved in the translation of picornavirus mRNAs and some cellular mRNAs .

<dna>IRES elements</dna> have been proposed to be involved in the translation of <rna>picornavirus mRNAs</rna> and some <rna>cellular mRNAs</rna> .


Internal ribosome binding likely requires the interaction of trans-acting factors that recognize both the mRNA and the ribosomal complex .

Internal ribosome binding likely requires the interaction of <protein>trans-acting factors</protein> that recognize both the <rna>mRNA</rna> and the <protein>ribosomal complex</protein> .


Five cellular proteins ( p52 , p57 , p70 , p72 , and p100 ) cross-link the EMCV IRES or fragments of the IRES .

Five <protein>cellular proteins</protein> ( <protein>p52</protein> , <protein>p57</protein> , <protein>p70</protein> , <protein>p72</protein> , and <protein>p100</protein> ) cross-link the EMCV <dna>IRES</dna> or fragments of the <dna>IRES</dna> .


For one of these proteins , p57 , binding to the IRES correlates with translation .

For one of these proteins , <protein>p57</protein> , binding to the <dna>IRES</dna> correlates with translation .


Recently , p57 was identified to be very similar , if not identical , to polypyrimidine tract-binding protein .

Recently , <protein>p57</protein> was identified to be very similar , if not identical , to <protein>polypyrimidine tract-binding protein</protein> .


On the basis of cross-linking results with 21 different EMCV IRES fragments and cytoplasmic HeLa extract or rabbit reticulocyte lysate as the source of polypeptides , consensus binding sites for p52 , p57 , p70 , and p100 are proposed .

On the basis of cross-linking results with 21 different <dna>EMCV IRES fragments</dna> and cytoplasmic HeLa extract or rabbit reticulocyte lysate as the source of polypeptides , <dna>consensus binding sites</dna> for <protein>p52</protein> , <protein>p57</protein> , <protein>p70</protein> , and <protein>p100</protein> are proposed .


It is suggested that each of these proteins recognizes primarily a structural feature of the RNA rather than a specific sequence .


A novel heterodimerization partner for thyroid hormone receptor .

A novel <protein>heterodimerization partner</protein> for <protein>thyroid hormone receptor</protein> .


Peroxisome proliferator-activated receptor .

<protein>Peroxisome proliferator-activated receptor</protein> .


Retinoid-like receptors play a central role in hormonal responses by forming heterodimers with other nuclear hormone receptors .

<protein>Retinoid-like receptors</protein> play a central role in hormonal responses by forming <protein>heterodimers</protein> with other <protein>nuclear hormone receptors</protein> .


In this study we have identified the peroxisome proliferator-activated receptor ( PPAR ) as a new thyroid hormone receptor ( THR ) auxiliary nuclear protein , heterodimerizing with THR in solution .

In this study we have identified the <protein>peroxisome proliferator-activated receptor</protein> ( <protein>PPAR</protein> ) as a new <protein>thyroid hormone receptor ( THR ) auxiliary nuclear protein</protein> , heterodimerizing with <protein>THR</protein> in solution .


Although these heterodimers do not recognize a classical thyroid hormone response element ( TRE ) characterized by direct repeat separated by four nucleotides ( DR+4 ) , PPAR behaves as a dominant negative regulator of thyroid hormone ( TH ) action .

Although these <protein>heterodimers</protein> do not recognize a classical <dna>thyroid hormone response element</dna> ( <dna>TRE</dna> ) characterized by direct repeat separated by four nucleotides ( <dna>DR+4</dna> ) , <protein>PPAR</protein> behaves as a dominant negative regulator of thyroid hormone ( TH ) action .


However , a TH-dependent positive effect is elicited by selective interaction of the THR beta-PPAR but not the THR alpha-PPAR heterodimer with a novel TRE ( DR+2 ) .

However , a TH-dependent positive effect is elicited by selective interaction of the <protein>THR beta-PPAR</protein> but not the <protein>THR alpha-PPAR heterodimer</protein> with a novel <dna>TRE</dna> ( <dna>DR+2</dna> ) .


The critical region of THR beta was mapped to 3 amino acids in the distal box of the DNA binding domain .

The critical region of <protein>THR</protein> beta was mapped to 3 amino acids in the <protein>distal box</protein> of the <protein>DNA binding domain</protein> .


Hence , PPAR can positively or negatively influence TH action depending on TRE structure and THR isotype .

Hence , <protein>PPAR</protein> can positively or negatively influence TH action depending on <dna>TRE</dna> structure and <protein>THR isotype</protein> .


Comparison of retinoic acid and phorbol myristate acetate as inducers of monocytic differentiation .


Several human myeloid leukemia cell lines growing in vitro can be induced to differentiate to more mature monocyte/macrophage-like cells by treatment with protein kinase C -activating phorbol esters , such as PMA .

Several <cell_line>human myeloid leukemia cell lines</cell_line> growing in vitro can be induced to differentiate to more mature <cell_type>monocyte/macrophage-like cells</cell_type> by treatment with <protein>protein kinase C</protein> -activating phorbol esters , such as PMA .


In addition to PMA , cells of the THP-1 myeloid leukemia cell line acquire macrophage-like characteristics after treatment with all-trans retinoic acid ( RA ) .

In addition to PMA , cells of the <cell_line>THP-1 myeloid leukemia cell line</cell_line> acquire macrophage-like characteristics after treatment with all-trans retinoic acid ( RA ) .


To analyze the signal transduction mechanisms induced by RA , we first compared the effects of PMA and RA on the expression of genes which are known to be regulated during monocytic differentiation .


Both RA and PMA effectively down-regulated c-myc expression , while c-myb expression decreased only after PMA treatment .

Both RA and PMA effectively down-regulated <dna>c-myc</dna> expression , while <dna>c-myb</dna> expression decreased only after PMA treatment .


Expression of the beta 2-integrin genes , CD11a and CD11b , was clearly increased after both of these treatments .

Expression of the <dna>beta 2-integrin genes</dna> , <dna>CD11a</dna> and <dna>CD11b</dna> , was clearly increased after both of these treatments .


Their effects on the src-family tyrosine kinase genes were different : hck expression was similarly induced by these agents but lyn expression was stronger and more rapid after RA treatment .

Their effects on the <dna>src-family tyrosine kinase genes</dna> were different : <dna>hck</dna> expression was similarly induced by these agents but lyn expression was stronger and more rapid after RA treatment .


RA also enhanced lyn mRNA production rapidly in HL-60 , indicating that the activation of lyn gene expression is common in monocytic and granulocytic maturation of myeloid leukemia cells .

RA also enhanced <rna>lyn mRNA</rna> production rapidly in <cell_line>HL-60</cell_line> , indicating that the activation of <dna>lyn gene</dna> expression is common in monocytic and granulocytic maturation of <cell_type>myeloid leukemia cells</cell_type> .


To examine whether the AP-1 enhancer activity is involved in RA-induced monocytic differentiation , THP-1 cells were transiently transfected with a chloramphenicol acetyl transferase ( CAT ) -reporter gene containing 5 copies of the AP-1 binding sites .

To examine whether the <dna>AP-1 enhancer</dna> activity is involved in RA-induced monocytic differentiation , <cell_line>THP-1 cells</cell_line> were transiently transfected with a <dna>chloramphenicol acetyl transferase ( CAT ) -reporter gene</dna> containing 5 copies of the <dna>AP-1 binding sites</dna> .


In contrast to PMA , RA did not induce any CAT activity in these cells , thus suggesting that the RA-induced changes in the expression of those genes described above were not dependent on the AP-1 enhancer activity .

In contrast to PMA , RA did not induce any <protein>CAT</protein> activity in these cells , thus suggesting that the RA-induced changes in the expression of those genes described above were not dependent on the <dna>AP-1 enhancer</dna> activity .


An active v-abl protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement .

An active <protein>v-abl protein tyrosine kinase</protein> blocks <dna>immunoglobulin light-chain gene</dna> rearrangement .


Lymphoid cells transformed by Abelson murine leukemia virus have provided one of the classic models for study of early B-cell development and immunoglobulin rearrangement .

<cell_type>Lymphoid cells</cell_type> transformed by Abelson murine leukemia virus have provided one of the classic models for study of early B-cell development and <protein>immunoglobulin</protein> rearrangement .


Most of these cells have rearranged their heavy-chain locus but not their light chain genes , suggesting that an active v-abl protein interferes with this differentiation step .

Most of these cells have rearranged their <dna>heavy-chain locus</dna> but not their <dna>light chain genes</dna> , suggesting that an active <protein>v-abl protein</protein> interferes with this differentiation step .


To test this hypothesis , light-chain gene structure was examined in pre-B cells transformed by temperature-sensitive mutants of the Abelson virus and in derivatives that survive at the nonpermissive temperature because they express a human BCL-2 gene .

To test this hypothesis , <dna>light-chain gene structure</dna> was examined in <cell_line>pre-B cells</cell_line> transformed by temperature-sensitive mutants of the Abelson virus and in derivatives that survive at the nonpermissive temperature because they express a <dna>human BCL-2 gene</dna> .


Our studies reveal that inactivation of the v-abl protein tyrosine kinase triggers high-frequency rearrangement of kappa and lambda light-chain genes .

Our studies reveal that inactivation of the <protein>v-abl protein tyrosine kinase</protein> triggers high-frequency rearrangement of <dna>kappa and lambda light-chain genes</dna> .


These events are accompanied by marked increases in the expression of RAG-1 and RAG-2 RNAs .

These events are accompanied by marked increases in the expression of <rna>RAG-1 and RAG-2 RNAs</rna> .


These increases occur in the absence of protein synthesis but are dependent on inactivation of the v-abl protein tyrosine kinase .

These increases occur in the absence of protein synthesis but are dependent on inactivation of the <protein>v-abl protein tyrosine kinase</protein> .


As documented in the accompanying paper ( Klug et al. , this issue ) , an active v-abl protein also suppresses the activity of NF-kappa B/rel and expression controlled by the kappa intron enhancer .

As documented in the accompanying paper ( Klug et al. , this issue ) , an active <protein>v-abl protein</protein> also suppresses the activity of <protein>NF-kappa B/rel</protein> and expression controlled by the <dna>kappa intron enhancer</dna> .


Together these data demonstrate that the v-abl protein specifically interferes with light-chain gene rearrangement by suppressing at least two pathways essential for this stage of B-cell differentiation and suggest that tyrosine phosphorylation is important in regulating RAG gene expression .

Together these data demonstrate that the <protein>v-abl protein</protein> specifically interferes with <dna>light-chain gene</dna> rearrangement by suppressing at least two pathways essential for this stage of <cell_type>B-cell</cell_type> differentiation and suggest that tyrosine phosphorylation is important in regulating <dna>RAG gene</dna> expression .


Calcium signalling in T cells stimulated by a cyclophilin B-binding protein .

Calcium signalling in <cell_type>T cells</cell_type> stimulated by a <protein>cyclophilin B-binding protein</protein> .


The immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the T-cell receptor ( TCR ) that normally leads to T-cell activation .

The immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the <protein>T-cell receptor</protein> ( <protein>TCR</protein> ) that normally leads to T-cell activation .


When bound to cyclophilin , cyclosporin A binds and inactivates the key signalling intermediate calcineurin .

When bound to <protein>cyclophilin</protein> , cyclosporin A binds and inactivates the key signalling intermediate <protein>calcineurin</protein> .


To identify potential cellular homologues of cyclosporin A that might regulate calcium signalling , we have cloned human genes encoding cyclophilin B-binding-proteins using the yeast two-hybrid system .

To identify potential cellular homologues of cyclosporin A that might regulate calcium signalling , we have cloned human genes encoding <protein>cyclophilin B-binding-proteins</protein> using the yeast two-hybrid system .


One gene product , when overexpressed in Jurkat T cells , specifically induced transcription from the interleukin-2 enhancer , by activating the T-cell-specific transcription factors NF-AT and NF-IL2A .

One gene product , when overexpressed in <cell_line>Jurkat T cells</cell_line> , specifically induced transcription from the <dna>interleukin-2 enhancer</dna> , by activating the <protein>T-cell-specific transcription factors</protein> <protein>NF-AT</protein> and <protein>NF-IL2A</protein> .


This protein , termed calcium-signal modulating cyclophilin ligand ( CAML ) , acts downstream of the TCR and upstream of calcineurin by causing an influx of calcium .

This protein , termed <protein>calcium-signal modulating cyclophilin ligand</protein> ( <protein>CAML</protein> ) , acts downstream of the <protein>TCR</protein> and upstream of <protein>calcineurin</protein> by causing an influx of calcium .


CAML appears to be a new participant in the calcium-signal transduction pathway , implicating cyclophilin B in calcium signalling , even in the absence of cyclosporin .

<protein>CAML</protein> appears to be a new participant in the calcium-signal transduction pathway , implicating <protein>cyclophilin B</protein> in calcium signalling , even in the absence of cyclosporin .


Expression and genomic configuration of GM-CSF , IL-3 , M-CSF receptor ( C-FMS ) , early growth response gene-1 ( EGR-1 ) and M-CSF genes in primary myelodysplastic syndromes .

Expression and genomic configuration of <protein>GM-CSF</protein> , <protein>IL-3</protein> , <protein>M-CSF receptor</protein> ( <protein>C-FMS</protein> ) , <dna>early growth response gene-1</dna> ( <dna>EGR-1</dna> ) and <dna>M-CSF genes</dna> in primary myelodysplastic syndromes .


Peripheral blood mononuclear cells from seventeen patients with primary myelodysplastic syndromes ( MDS ) in advanced stage were enriched for blasts and tested for ( 1 ) karyotype , ( 2 ) genomic configuration and ( 3 ) expression of IL-3 , GM-CSF , FMS and EGR-1 genes which are all located on the long arm of chromosome 5 .

Peripheral blood mononuclear cells from seventeen patients with primary myelodysplastic syndromes ( MDS ) in advanced stage were enriched for <cell_type>blasts</cell_type> and tested for ( 1 ) karyotype , ( 2 ) genomic configuration and ( 3 ) expression of <dna>IL-3 , GM-CSF , FMS and EGR-1 genes</dna> which are all located on the <dna>long arm of chromosome 5</dna> .


The expression of the M-CSF gene , that has been recently reassigned to the short arm of chromosome 1 ( lp ) , was also investigated .

The expression of the <dna>M-CSF gene</dna> , that has been recently reassigned to the <dna>short arm of chromosome 1</dna> ( <dna>lp</dna> ) , was also investigated .


Aims of the study were to ( 1 ) assess the potential role of the expression of these genes in the maintenance and expansion of the neoplastic clones and ( 2 ) search for constitutional losses or rearrangements of one allele followed by a deletion of the second allele of the same genes in the leukemic cells .

Aims of the study were to ( 1 ) assess the potential role of the expression of these genes in the maintenance and expansion of the <cell_line>neoplastic clones</cell_line> and ( 2 ) search for constitutional losses or rearrangements of one <dna>allele</dna> followed by a deletion of the second <dna>allele</dna> of the same genes in the <cell_type>leukemic cells</cell_type> .


The latter issue was investigated by comparing , in 8 cases , constitutive DNA from skin fibroblasts with leukemic DNA .

The latter issue was investigated by comparing , in 8 cases , <dna>constitutive DNA</dna> from <cell_type>skin fibroblasts</cell_type> with <dna>leukemic DNA</dna> .


Eleven of the 17 patients had abnormal karyotypes .