We performed an analysis of the mechanisms by which two PKC inhibitors , Calphostin C and Staurosporine , prevent the FN -induced IL-1beta response .

We performed an analysis of the mechanisms by which two <protein>PKC</protein> inhibitors , Calphostin C and Staurosporine , prevent the <protein>FN</protein> -induced <protein>IL-1beta</protein> response .


Both inhibitors blocked the secretion of IL-1beta protein into the media of peripheral blood mononuclear cells exposed to FN .

Both inhibitors blocked the secretion of <protein>IL-1beta protein</protein> into the media of <cell_type>peripheral blood mononuclear cells</cell_type> exposed to <protein>FN</protein> .


Immunoprecipitation analysis revealed that unde3r these circumstances , Calphostin C inhibited the production of IL-1beta protein , whereas Staurosporine allowed protein production , but inhibited its secretion .

Immunoprecipitation analysis revealed that unde3r these circumstances , Calphostin C inhibited the production of <protein>IL-1beta protein</protein> , whereas Staurosporine allowed protein production , but inhibited its secretion .


To determine the mechanisms responsible for these differences , we turned to human U937 promonocytic cells .

To determine the mechanisms responsible for these differences , we turned to <cell_line>human U937 promonocytic cells</cell_line> .


U937 cells transfected with the human full-length IL-1beta promoter connected to a luciferase reporter gene were submitted to transcription assays , Northern blotting , and DNA electrophoresis mobility gel shift assays .

U937 cells transfected with the human <dna>full-length IL-1beta promoter</dna> connected to a <dna>luciferase reporter gene</dna> were submitted to transcription assays , Northern blotting , and DNA electrophoresis mobility gel shift assays .


These studies revealed that Calphostin C inhibited the nuclear translocation of the transcription factor activator protein-1 ( AP-1 ) which is considered necessary for FN induction of IL-1beta gene transcription , and prevented the transcription of the IL-1beta gene .

These studies revealed that Calphostin C inhibited the nuclear translocation of the <protein>transcription factor activator protein-1</protein> ( <protein>AP-1</protein> ) which is considered necessary for <protein>FN</protein> induction of <protein>IL-1beta</protein> gene transcription , and prevented the transcription of the <dna>IL-1beta gene</dna> .


In contrast , Staurosporine alone induced AP-1 translocation and stimulation of the gene .

In contrast , Staurosporine alone induced <protein>AP-1</protein> translocation and stimulation of the gene .


Overall , our data indicate that Calphostin C prevents the transcription of the IL-1beta gene thereby inhibiting protein synthesis .

Overall , our data indicate that Calphostin C prevents the transcription of the <dna>IL-1beta gene</dna> thereby inhibiting protein synthesis .


Based on the high specificity of this compound for PKC , we conclude that PKC is necessary for FN -induced IL-1beta protein production .

Based on the high specificity of this compound for <protein>PKC</protein> , we conclude that <protein>PKC</protein> is necessary for <protein>FN</protein> -induced <protein>IL-1beta</protein> protein production .


In contrast , Staurosporine prevented secretion of IL-1beta by unknown mechanisms

In contrast , Staurosporine prevented secretion of <protein>IL-1beta</protein> by unknown mechanisms


The carboxyl-terminal cytoplasmic domain of CD36 is required for oxidized low-density lipoprotein modulation of NF-kappaB activity by tumor necrosis factor-alpha .

The <protein>carboxyl-terminal cytoplasmic domain</protein> of <protein>CD36</protein> is required for oxidized low-density lipoprotein modulation of <protein>NF-kappaB</protein> activity by <protein>tumor necrosis factor-alpha</protein> .


The binding of oxidized low-density lipoprotein ( Ox LDL ) by monocyte -macrophages causes pleiotropic effects , including changes in gene expression , and is thought to represent an early event in atherogenesis .

The binding of oxidized low-density lipoprotein ( Ox LDL ) by <cell_type>monocyte</cell_type> <cell_type>-macrophages</cell_type> causes pleiotropic effects , including changes in gene expression , and is thought to represent an early event in atherogenesis .


The integral membrane glycoprotein CD36 appears to play a physiological role in binding and uptake of Ox LDL by monocyte-macrophages , although the molecular events associated with CD36 -Ox LDL interaction are unknown .

The integral membrane <protein>glycoprotein CD36</protein> appears to play a physiological role in binding and uptake of Ox LDL by <cell_type>monocyte-macrophages</cell_type> , although the molecular events associated with <protein>CD36</protein> -Ox LDL interaction are unknown .


To approach this issue , we used CD36 transfected Chinese hampster ovary ( CHO ) cells , exposed them to Ox LDL , and determined changes in the activity of the transcription factor NF-kappaB .

To approach this issue , we used <protein>CD36</protein> transfected <cell_type>Chinese hampster ovary ( CHO ) cells</cell_type> , exposed them to Ox LDL , and determined changes in the activity of the <protein>transcription factor</protein> <protein>NF-kappaB</protein> .


We report here that Ox LDL enhanced DNA binding activity of nuclear extracts to an NF-kappaB sequence following activation of CD36-producing CHO cells with the proinflammatory cytokine tumor necrosis factor-alpha ( TNF-alpha ) .

We report here that Ox LDL enhanced DNA binding activity of nuclear extracts to an <dna>NF-kappaB sequence</dna> following activation of <cell_line>CD36-producing CHO cells</cell_line> with the <protein>proinflammatory cytokine</protein> <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) .


This enhanced DNA binding activity was inhibited by coincubation of CD36 transfected cells with the human CD36-specific antibody OKM5 .

This enhanced DNA binding activity was inhibited by coincubation of <protein>CD36</protein> transfected cells with the <protein>human CD36-specific antibody</protein> <protein>OKM5</protein> .


We also determined that activation of NF-kappaB DNA binding activity required an intact carboxyl-terminal cytoplasmic segment on CD36 .

We also determined that activation of <protein>NF-kappaB</protein> DNA binding activity required an intact <protein>carboxyl-terminal cytoplasmic segment</protein> on <protein>CD36</protein> .


Our results support the idea that human CD36 mediates signal transduction events in response to Ox LDL .

Our results support the idea that <protein>human CD36</protein> mediates signal transduction events in response to Ox LDL .


TRAMP , a novel apoptosis-mediating receptor with sequence homology to tumor necrosis factor receptor 1 and Fas ( Apo-1/CD95 ) .

<protein>TRAMP</protein> , a novel <protein>apoptosis-mediating receptor</protein> with sequence homology to <protein>tumor necrosis factor receptor 1</protein> and <protein>Fas</protein> ( <protein>Apo-1/CD95</protein> ) .


A novel member of the tumor necrosis factor ( TNF ) receptor family , designated TRAMP , has been identified .

A novel member of the <protein>tumor necrosis factor ( TNF ) receptor family</protein> , designated <protein>TRAMP</protein> , has been identified .


The structural organization of the 393 amino acid long human TRAMP is most homologous to TNF receptor 1 .

The structural organization of the <protein>393 amino acid long human TRAMP</protein> is most homologous to <protein>TNF receptor 1</protein> .


TRAMP is abundantly expressed on thymocytes and lymphocytes .

<protein>TRAMP</protein> is abundantly expressed on <cell_type>thymocytes</cell_type> and <cell_type>lymphocytes</cell_type> .


Its extracellular domain is composed of four cysteine-rich domains , and the cytoplasmic region contains a death domain known to signal apoptosis .

Its extracellular domain is composed of four <protein>cysteine-rich domains</protein> , and the <protein>cytoplasmic region</protein> contains a <protein>death domain</protein> known to signal apoptosis .


Overexpression of TRAMP leads to two major responses , NF-kappaB activation and apoptosis .

Overexpression of <protein>TRAMP</protein> leads to two major responses , <protein>NF-kappaB</protein> activation and apoptosis .


TRAMP -induced cell death is inhibited by an inhibitor of ICE-like proteases , but not by Bcl-2 .

<protein>TRAMP</protein> -induced cell death is inhibited by an inhibitor of <protein>ICE-like proteases</protein> , but not by <protein>Bcl-2</protein> .


In addition , TRAMP does not appear to interact with any of the known apoptosis-inducing ligands of the TNF family .

In addition , <protein>TRAMP</protein> does not appear to interact with any of the known <protein>apoptosis-inducing ligands</protein> of the <protein>TNF family</protein> .


The state of maturation of monocytes into macrophages determines the effects of IL-4 and IL-13 on HIV replication .

The state of maturation of <cell_type>monocytes</cell_type> into <cell_type>macrophages</cell_type> determines the effects of <protein>IL-4</protein> and <protein>IL-13</protein> on HIV replication .


The molecular mechanisms of the effects of IL-4 and IL-13 on HIV infection in human monocytes as they matured into monocyte-derived macrophages over 7 days were investigated using HIV-1 ( BaL ) , and low passage clinical strains .

The molecular mechanisms of the effects of <protein>IL-4</protein> and <protein>IL-13</protein> on HIV infection in <cell_type>human monocytes</cell_type> as they matured into <cell_type>monocyte-derived macrophages</cell_type> over 7 days were investigated using HIV-1 ( BaL ) , and low passage clinical strains .


IL-4 and IL-13 up-regulated the expression of both genomic and spliced HIV mRNA in monocytes cultured on Teflon , as determined by Northern analysis and p24 Ag assay .

<protein>IL-4</protein> and <protein>IL-13</protein> up-regulated the expression of both genomic and spliced <rna>HIV mRNA</rna> in <cell_type>monocytes</cell_type> cultured on Teflon , as determined by Northern analysis and <protein>p24 Ag</protein> assay .


Using a nuclear run-on assay , IL-4 stimulation was shown to enhance transcription by two- to threefold .

Using a nuclear run-on assay , <protein>IL-4</protein> stimulation was shown to enhance transcription by two- to threefold .


IL-4 stimulated nuclear factor-kappaB nuclear translocation and binding before enhancement of HIV RNA expression .

<protein>IL-4</protein> stimulated <protein>nuclear factor-kappaB</protein> nuclear translocation and binding before enhancement of <rna>HIV RNA</rna> expression .


Conversely , IL-4 and IL-13 markedly and significantly inhibited HIV replication at the transcriptional level in monocyte-derived macrophages , and this occurred whether these cytokines were added before or after HIV infection .

Conversely , <protein>IL-4</protein> and <protein>IL-13</protein> markedly and significantly inhibited HIV replication at the transcriptional level in <cell_type>monocyte-derived macrophages</cell_type> , and this occurred whether these <protein>cytokines</protein> were added before or after HIV infection .


The reversal from stimulation to inhibition occurred after 3 to 5 days of adherence to plastic .


IL-4 had no significant effect on HIV reverse transcription .

<protein>IL-4</protein> had no significant effect on HIV reverse transcription .


The effect of both cytokines on the monocyte maturation/differentiation ( CD11b , CD13 , and CD26 ) and other macrophage markers ( CD14 and CD68 ) was examined .

The effect of both <protein>cytokines</protein> on the monocyte maturation/differentiation ( <protein>CD11b</protein> , <protein>CD13</protein> , and <protein>CD26</protein> ) and other <protein>macrophage markers</protein> ( <protein>CD14</protein> and <protein>CD68</protein> ) was examined .


IL-4 enhanced CD11b , but inhibited CD26 expression and delayed CD13 loss .

<protein>IL-4</protein> enhanced <protein>CD11b</protein> , but inhibited <protein>CD26</protein> expression and delayed <protein>CD13</protein> loss .


IL-13 had similar effects on CD11b and CD13 , but no effect on CD26 .

<protein>IL-13</protein> had similar effects on <protein>CD11b</protein> and <protein>CD13</protein> , but no effect on <protein>CD26</protein> .


Hence , these cytokines do not simply enhance monocyte differentiation , but have complex and slightly divergent effects that impact on HIV replication probably through cell signaling pathways and nuclear factor-kappaB translocation .

Hence , these <protein>cytokines</protein> do not simply enhance monocyte differentiation , but have complex and slightly divergent effects that impact on HIV replication probably through cell signaling pathways and <protein>nuclear factor-kappaB</protein> translocation .


Mice lacking the transcription factor CIITA -- a second look .

Mice lacking the <protein>transcription factor</protein> <protein>CIITA</protein> -- a second look .


We have generated a second line of mice lacking a transcription factor thought to be a critical regulator of MHC class II gene expression , CIITA ( for class II transactivator ) .

We have generated a second line of mice lacking a <protein>transcription factor</protein> thought to be a critical regulator of <dna>MHC class II gene</dna> expression , <protein>CIITA</protein> ( for class II <protein>transactivator</protein> ) .


Our and the previously published lines differ in the deletion that was engineered and by the fact that we removed the neomycin-resistance promoter and structural gene via the cre-loxP recombination system .

Our and the previously published lines differ in the deletion that was engineered and by the fact that we removed the <dna>neomycin-resistance promoter</dna> and <dna>structural gene</dna> via the cre-loxP recombination system .


Characterization of our line led to two new findings .


First , a substantial number of cells can express class II molecules in the absence of CIITA , albeit at 5-fold reduced levels , most notably dendritic cells in s.c. lymph nodes ; therefore , the CIITA gene can not be an absolute ' master gene ' controlling the expression of class II molecules , as had been thought .

First , a substantial number of cells can express <protein>class II molecules</protein> in the absence of <protein>CIITA</protein> , albeit at 5-fold reduced levels , most notably <cell_type>dendritic cells</cell_type> in s.c. lymph nodes ; therefore , the <dna>CIITA gene</dna> can not be an absolute ' <dna>master gene</dna> ' controlling the expression of <protein>class II molecules</protein> , as had been thought .


Second , in contrast to recent results on human cell lines , CIITA is not critically involved in the IFN-gamma -induced up-regulation of MHC class I genes .

Second , in contrast to recent results on <cell_line>human cell lines</cell_line> , <protein>CIITA</protein> is not critically involved in the <protein>IFN-gamma</protein> -induced up-regulation of <dna>MHC class I genes</dna> .


Interleukin-10 stabilizes inhibitory kappaB-alpha in human monocytes .

<protein>Interleukin-10</protein> stabilizes inhibitory <protein>kappaB-alpha</protein> in <cell_type>human monocytes</cell_type> .


Interleukin-10 ( IL-10 ) protects animals from lethal endotoxemia .

<protein>Interleukin-10</protein> ( <protein>IL-10</protein> ) protects animals from lethal endotoxemia .


This beneficial effect is mediated , in part , by inhibition of inflammatory cytokine production , including tumor necrosis factor-alpha ( TNF-alpha ) .

This beneficial effect is mediated , in part , by inhibition of <protein>inflammatory cytokine</protein> production , including <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) .


Evidence suggests that IL-10 may inhibit activation of the transcription factor nuclear factor-kappaB ( NF-kappaB ) through an unknown mechanism .

Evidence suggests that <protein>IL-10</protein> may inhibit activation of the <protein>transcription factor</protein> <protein>nuclear factor-kappaB</protein> ( <protein>NF-kappaB</protein> ) through an unknown mechanism .


NF-kappaB activation in response to inflammatory signals is dependent upon degradation of its associated inhibitory peptide , inhibitory kappaB-alpha ( IkappaB-alpha ) .

<protein>NF-kappaB</protein> activation in response to inflammatory signals is dependent upon degradation of its associated inhibitory peptide , <protein>inhibitory kappaB-alpha</protein> ( <protein>IkappaB-alpha</protein> ) .


We hypothesized that IL-10 prevents human monocyte NF-kappaB activation and resultant TNF-alpha production by stabilization of IkappaB-alpha .

We hypothesized that <protein>IL-10</protein> prevents human monocyte <protein>NF-kappaB</protein> activation and resultant <protein>TNF-alpha</protein> production by stabilization of <protein>IkappaB-alpha</protein> .


The purpose of this study was to determine the effect of IL-10 on lipopolysaccharide ( LPS ) -induced human monocyte TNF-alpha production , NF-kappaB activation , and IkappaB-alpha degradation .

The purpose of this study was to determine the effect of <protein>IL-10</protein> on lipopolysaccharide ( LPS ) -induced human monocyte <protein>TNF-alpha</protein> production , <protein>NF-kappaB</protein> activation , and <protein>IkappaB-alpha</protein> degradation .


Monocytes were isolated from human donors .


Cells were stimulated with endotoxin ( LPS , 100 ng/mL ) with and without human IL-10 ( 10 ng/mL ) .

Cells were stimulated with <protein>endotoxin</protein> ( LPS , 100 ng/mL ) with and without human <protein>IL-10</protein> ( 10 ng/mL ) .


Following stimulation , TNF-alpha was measured in cell supernatants by ELISA , NF-kappaB activity by electrophoretic mobility shift assay , and IkappaB-alpha levels by Western blot .

Following stimulation , <protein>TNF-alpha</protein> was measured in cell supernatants by ELISA , <protein>NF-kappaB</protein> activity by electrophoretic mobility shift assay , and <protein>IkappaB-alpha</protein> levels by Western blot .


We observed that after LPS stimulation of human monocytes , TNF-alpha increased to 798+/-67 pg/mL ( p < .001 versus control ) .

We observed that after LPS stimulation of <cell_type>human monocytes</cell_type> , <protein>TNF-alpha</protein> increased to 798+/-67 pg/mL ( p < .001 versus control ) .


IL-10 attenuated LPS-stimulated TNF-alpha production ( 297+/-54 ; p < .001 versus LPS alone ) .

<protein>IL-10</protein> attenuated LPS-stimulated <protein>TNF-alpha</protein> production ( 297+/-54 ; p < .001 versus LPS alone ) .


After LPS stimulation in human monocytes , IkappaB-alpha protein levels decreased , and NF-kappaB DNA binding increased .

After LPS stimulation in <cell_type>human monocytes</cell_type> , <protein>IkappaB-alpha</protein> protein levels decreased , and <protein>NF-kappaB</protein> DNA binding increased .


IL-10 pretreatment prevented LPS-induced decreases in IkappaB-alpha protein levels and attenuated NF-kappaB DNA binding .

<protein>IL-10</protein> pretreatment prevented LPS-induced decreases in <protein>IkappaB-alpha</protein> protein levels and attenuated <protein>NF-kappaB</protein> DNA binding .


IL-10 appears to prevent activation of NF-kappaB by preserving IkappaB-alpha protein levels , leading to a reduction in TNF-alpha release .

<protein>IL-10</protein> appears to prevent activation of <protein>NF-kappaB</protein> by preserving <protein>IkappaB-alpha</protein> protein levels , leading to a reduction in <protein>TNF-alpha</protein> release .


Down-regulation of human granzyme B expression by glucocorticoids .

Down-regulation of human <protein>granzyme B</protein> expression by glucocorticoids .


Dexamethasone inhibits binding to the Ikaros and AP-1 regulatory elements of the granzyme B promoter .

Dexamethasone inhibits binding to the <protein>Ikaros</protein> and <dna>AP-1 regulatory elements</dna> of the <dna>granzyme B promoter</dna> .


The serine protease granzyme B is an essential component of the granule exocytosis pathway , a major apoptotic mechanism used by cytotoxic T lymphocytes and natural killer cells to induce target cell apoptosis .

The <protein>serine protease granzyme B</protein> is an essential component of the granule exocytosis pathway , a major apoptotic mechanism used by <cell_type>cytotoxic T lymphocytes</cell_type> and <cell_type>natural killer cells</cell_type> to induce target cell apoptosis .


Granzyme B gene transcription is induced in activated lymphocytes upon antigenic stimulation , and several regulatory regions including CBF , AP-1 , and Ikaros binding sites have been shown to be essential in the control of granzyme B promoter activation .

Granzyme B gene transcription is induced in activated <cell_type>lymphocytes</cell_type> upon antigenic stimulation , and several <dna>regulatory regions</dna> including <protein>CBF</protein> , <protein>AP-1</protein> , and <dna>Ikaros binding sites</dna> have been shown to be essential in the control of <dna>granzyme B promoter</dna> activation .


Dexamethasone , a glucocorticoid that is widely used as an immunomodulatory and anti-inflammatory agent , inhibits granzyme B mRNA transcript in phytohemagglutinin-activated peripheral blood mononuclear cells .

Dexamethasone , a glucocorticoid that is widely used as an immunomodulatory and anti-inflammatory agent , inhibits <rna>granzyme B mRNA transcript</rna> in <cell_type>phytohemagglutinin-activated peripheral blood mononuclear cells</cell_type> .


Transfection of a reporter construct containing the -148 to +60 region of the human granzyme B promoter demonstrated that this region was the target for dexamethasone repression .

Transfection of a reporter construct containing the <dna>-148 to +60 region</dna> of the human <dna>granzyme B promoter</dna> demonstrated that this region was the target for dexamethasone repression .


Mutation of Ikaros or AP-1 binding sites in the context of the granzyme B promoter demonstrated that both sites participate in dexamethasone-mediated inhibition of the granzyme B promoter activity .

Mutation of <protein>Ikaros</protein> or <dna>AP-1 binding sites</dna> in the context of the <dna>granzyme B promoter</dna> demonstrated that both sites participate in dexamethasone-mediated inhibition of the <dna>granzyme B promoter</dna> activity .


Electromobility shift assay revealed that dexamethasone abolished the binding of nuclear transcription factors to the Ikaros binding site and reduced AP-1 binding activity .

Electromobility shift assay revealed that dexamethasone abolished the binding of <protein>nuclear transcription factors</protein> to the <dna>Ikaros binding site</dna> and reduced <protein>AP-1</protein> binding activity .


These results indicate that dexamethasone is able to abrogate the transcriptional activity of the human granzyme B gene promoter by inhibiting the binding of nuclear factors at the AP-1 and Ikaros sites .

These results indicate that dexamethasone is able to abrogate the transcriptional activity of the <dna>human granzyme B gene promoter</dna> by inhibiting the binding of <protein>nuclear factors</protein> at the <dna>AP-1 and Ikaros sites</dna> .


Glucocorticoid receptors on mononuclear leukocytes in polycystic ovary syndrome .

<protein>Glucocorticoid receptors</protein> on <cell_type>mononuclear leukocytes</cell_type> in polycystic ovary syndrome .


OBJECTIVE : Many studies have suggested that there is a possible hormonal dysregulation of hypothalamic-pituitary-adrenal ( HPA ) axis and an increased cortisol clearance in patients with polycystic ovary syndrome ( PCOS ) .


Therefore in this study , we have examined the role of glucocorticoid receptor/s ( GR ) characteristics in the developing of these abnormalities in patients with PCOS .

Therefore in this study , we have examined the role of <protein>glucocorticoid receptor/s</protein> ( <protein>GR</protein> ) characteristics in the developing of these abnormalities in patients with PCOS .


METHOD : For this purpose , the number and affinity of GR in peripheral mononuclear leukocytes ( MNL ) of 10 patients with PCOS and 10 healthy women ( controls ) were determined .

METHOD : For this purpose , the number and affinity of <protein>GR</protein> in peripheral <cell_type>mononuclear leukocytes</cell_type> ( MNL ) of 10 patients with PCOS and 10 healthy women ( controls ) were determined .


RESULTS : There were no significant differences in the number ( 6500+/-1001 sites/cell and 6352+/-1697 sites/cell , respectively ; P > 0.05 ) and affinity ( 3.93+/-0.89 nM and 4.49+/-0.71 nM , respectively ; P > 0.05 ) of GR between the PCOS patients and the controls .

RESULTS : There were no significant differences in the number ( 6500+/-1001 sites/cell and 6352+/-1697 sites/cell , respectively ; P > 0.05 ) and affinity ( 3.93+/-0.89 nM and 4.49+/-0.71 nM , respectively ; P > 0.05 ) of <protein>GR</protein> between the PCOS patients and the controls .


CONCLUSIONS : These results suggest that the alterations in the HPA axis and in the cortisol metabolism observed in PCOS are not related to GR deficiency .

CONCLUSIONS : These results suggest that the alterations in the HPA axis and in the cortisol metabolism observed in PCOS are not related to <protein>GR</protein> deficiency .


Heterogeneous expression of the lipocalin NGAL in primary breast cancers .

Heterogeneous expression of the <protein>lipocalin NGAL</protein> in primary breast cancers .


We have previously shown that neu oncogene-initiated rat mammary carcinomas uniquely over-express neu-related lipocalin ( NRL ) , a member of the calycin protein superfamily .

We have previously shown that neu oncogene-initiated rat mammary carcinomas uniquely over-express <protein>neu-related lipocalin</protein> ( <protein>NRL</protein> ) , a member of the <protein>calycin protein superfamily</protein> .


Here , we characterize the putative human homolog of NRL , neutrophil gelatinase-associated lipocalin ( NGAL ) .

Here , we characterize the <protein>putative human homolog</protein> of <protein>NRL</protein> , <protein>neutrophil gelatinase-associated lipocalin</protein> ( <protein>NGAL</protein> ) .


ngal gene expression was found at moderate levels in only 2 of 17 human tissues examined , breast and lung .


When breast cancers were examined for NGAL mRNA and protein levels , they were found to exhibit heterogeneous expression .


NGAL levels varied in these tumors from undetectable to exceeding those in normal breast parenchyma .

<protein>NGAL</protein> levels varied in these tumors from undetectable to exceeding those in normal breast parenchyma .


Immuno-histochemical analysis confirmed the presence of NGAL within breast carcinoma cells but detected only low levels of this protein in normal ductal epithelium .

Immuno-histochemical analysis confirmed the presence of <protein>NGAL</protein> within <cell_type>breast carcinoma cells</cell_type> but detected only low levels of this protein in normal ductal epithelium .


In contrast , large amounts of the protein were localized to the lumen of normal breast ducts in the vicinity of NGAL -expressing tumors .

In contrast , large amounts of the protein were localized to the lumen of normal breast ducts in the vicinity of <protein>NGAL</protein> -expressing tumors .


Interestingly , unlike NRL in rat mammary carcinomas , no significant association between NGAL expression and HER-2/neu activation was found in human breast tumors .

Interestingly , unlike <protein>NRL</protein> in rat mammary carcinomas , no significant association between <protein>NGAL</protein> expression and <protein>HER-2/neu</protein> activation was found in human breast tumors .


In contrast , a significant correlation between NGAL expression in breast cancer was found with several other markers of poor prognosis , including estrogen and progesterone receptor -negative status and high proliferation ( S-phase fraction ) .

In contrast , a significant correlation between <protein>NGAL</protein> expression in breast cancer was found with several other markers of poor prognosis , including estrogen and <protein>progesterone receptor</protein> -negative status and high proliferation ( S-phase fraction ) .


NGAL levels were stratified as high or low in breast cancers from a cohort of node-positive patients with known outcome .

<protein>NGAL</protein> levels were stratified as high or low in breast cancers from a cohort of node-positive patients with known outcome .


No significant association between NGAL expression and disease-free or overall survival was observed .

No significant association between <protein>NGAL</protein> expression and disease-free or overall survival was observed .


BASH , a novel signaling molecule preferentially expressed in B cells of the bursa of Fabricius .

<protein>BASH</protein> , a <protein>novel signaling molecule</protein> preferentially expressed in <cell_type>B cells</cell_type> of the bursa of Fabricius .


The bursa of Fabricius is a gut-associated lymphoid organ that is essential for the generation of a diversified B cell repertoire in the chicken .

The bursa of Fabricius is a gut-associated lymphoid organ that is essential for the generation of a diversified <cell_type>B cell repertoire</cell_type> in the chicken .


We describe here a novel gene preferentially expressed in bursal B cells .

We describe here a novel gene preferentially expressed in <cell_type>bursal B cells</cell_type> .


The gene encodes an 85-kDa protein , designated BASH ( B cell adaptor containing SH2 domain ) , that contains N-terminal acidic domains with SH2 domain-binding phosphotyrosine-based motifs , a proline-rich domain , and a C-terminal SH2 domain .

The gene encodes an <protein>85-kDa protein</protein> , designated <protein>BASH</protein> ( <protein>B cell adaptor containing SH2 domain</protein> ) , that contains <protein>N-terminal acidic domains</protein> with <protein>SH2 domain-binding phosphotyrosine-based motifs</protein> , a <protein>proline-rich domain</protein> , and a <protein>C-terminal SH2 domain</protein> .


BASH shows a substantial sequence similarity to SLP-76 , an adaptor protein functioning in TCR -signal transduction .

<protein>BASH</protein> shows a substantial sequence similarity to <protein>SLP-76</protein> , an adaptor protein functioning in <protein>TCR</protein> -signal transduction .


BASH becomes tyrosine-phosphorylated with the B cell Ag receptor ( BCR ) cross-link or by coexpression with Syk and Lyn and associates with signaling molecules including Syk and a putative chicken Shc homologue .

<protein>BASH</protein> becomes tyrosine-phosphorylated with the <protein>B cell Ag receptor</protein> ( <protein>BCR</protein> ) cross-link or by coexpression with <protein>Syk</protein> and <protein>Lyn</protein> and associates with <protein>signaling molecules</protein> including <protein>Syk</protein> and a <protein>putative chicken Shc homologue</protein> .


Overexpression of BASH results in suppression of the NF-AT activation induced by BCR -cross-linking .

Overexpression of <protein>BASH</protein> results in suppression of the <protein>NF-AT</protein> activation induced by <protein>BCR</protein> -cross-linking .


These findings suggest that BASH is involved in BCR -mediated signal transduction and could play a critical role in B cell development in the bursa .

These findings suggest that <protein>BASH</protein> is involved in <protein>BCR</protein> -mediated signal transduction and could play a critical role in B cell development in the bursa .


Granulocyte colony-stimulating factor activates a 72-kDa isoform of STAT3 in human neutrophils .

<protein>Granulocyte colony-stimulating factor</protein> activates a <protein>72-kDa isoform</protein> of <protein>STAT3</protein> in <cell_type>human neutrophils</cell_type> .


Granulocyte colony-stimulating factor ( G-CSF ) signaling involves activation of STATs , proteins that serve the dual function of signal transduction and activation of transcription .

<protein>Granulocyte colony-stimulating factor</protein> ( <protein>G-CSF</protein> ) signaling involves activation of <protein>STATs</protein> , proteins that serve the dual function of signal transduction and activation of transcription .


We previously demonstrated that G-CSF activated a distinct Stat3-like protein in immature and mature normal myeloid cells , StatG .

We previously demonstrated that <protein>G-CSF</protein> activated a distinct <protein>Stat3-like protein</protein> in <cell_type>immature and mature normal myeloid cells</cell_type> , <protein>StatG</protein> .


StatG in normal immature human myeloid cells , i.e . adult CD34+ bone marrow cells , was composed of Stat3beta .

<protein>StatG</protein> in <cell_type>normal immature human myeloid cells</cell_type> , i.e . <cell_type>adult CD34+ bone marrow cells</cell_type> , was composed of <protein>Stat3beta</protein> .


This investigation was undertaken to determine the composition of StatG in mature normal human myeloid cells , i.e . polymorphonuclear neutrophilic granulocytes ( PMN ) .

This investigation was undertaken to determine the composition of <protein>StatG</protein> in <cell_type>mature normal human myeloid cells</cell_type> , i.e . <cell_type>polymorphonuclear neutrophilic granulocytes</cell_type> ( <cell_type>PMN</cell_type> ) .


These studies revealed that the major protein in extracts of PMN activated by G-CSF to bind the high-affinity serum-inducible element ( hSIE ) is a 72-kDa protein that cross-reacts with Stat3 monoclonal antibody , which we have designated Stat3gamma .

These studies revealed that the <protein>major protein</protein> in extracts of <cell_type>PMN</cell_type> activated by <protein>G-CSF</protein> to bind the <dna>high-affinity serum-inducible element</dna> ( <dna>hSIE</dna> ) is a <protein>72-kDa protein</protein> that cross-reacts with <protein>Stat3 monoclonal antibody</protein> , which we have designated <protein>Stat3gamma</protein> .


Stat3gamma is derived from Stat3alpha by limited proteolysis and lacks the carboxyl-terminal portion of Stat3alpha .

<protein>Stat3gamma</protein> is derived from <protein>Stat3alpha</protein> by limited proteolysis and lacks the <protein>carboxyl-terminal portion</protein> of <protein>Stat3alpha</protein> .


Because this region of Stat3alpha is involved in transcriptional activation , our findings suggest the possibility that Stat3gamma may be transcriptionally inactive and may compete with Stat3alpha for Stat3 binding sites in these terminally differentiated myeloid cells

Because this region of <protein>Stat3alpha</protein> is involved in transcriptional activation , our findings suggest the possibility that <protein>Stat3gamma</protein> may be transcriptionally inactive and may compete with <protein>Stat3alpha</protein> for <dna>Stat3 binding sites</dna> in these <cell_type>terminally differentiated myeloid cells</cell_type>


Association between expression of intercellular adhesion molecule-1 and integration of human T-cell-leukemia virus type 1 in adult T-cell leukemia cells .

Association between expression of <protein>intercellular adhesion molecule-1</protein> and integration of human T-cell-leukemia virus type 1 in <cell_type>adult T-cell leukemia cells</cell_type> .


It is known that the expression levels of intercellular adhesion molecule-1 ( ICAM-1 ) in adult T cell leukemia ( ATL ) cells are high , whereas those in T-lymphoid cells are not .

It is known that the expression levels of <protein>intercellular adhesion molecule-1</protein> ( <protein>ICAM-1</protein> ) in <cell_type>adult T cell leukemia ( ATL ) cells</cell_type> are high , whereas those in <cell_type>T-lymphoid cells</cell_type> are not .


In order to investigate the factors that influence the induction of ICAM-1 molecules , Northern blot analysis to measure the expression level of ICAM-1 mRNAs and Southern blot hybridization to analyze the integration of human T-cell-leukemia virus type 1 ( HTLV-1 ) provirus were done .

In order to investigate the factors that influence the induction of <protein>ICAM-1</protein> molecules , Northern blot analysis to measure the expression level of <rna>ICAM-1 mRNAs</rna> and Southern blot hybridization to analyze the integration of human T-cell-leukemia virus type 1 ( HTLV-1 ) provirus were done .


The levels of ICAM-1 mRNA expression of ATL cells were generally higher than those of T-lymphoid cells .

The levels of <rna>ICAM-1 mRNA</rna> expression of <cell_line>ATL cells</cell_line> were generally higher than those of <cell_type>T-lymphoid cells</cell_type> .


However , ILT-mat cells and ATL16T ( - ) cells , although they were ATL cells , showed rather low surface ICAM-1 expression and ICAM-1 mRNA expression .

However , <cell_line>ILT-mat cells</cell_line> and <cell_line>ATL16T ( - ) cells</cell_line> , although they were <cell_line>ATL cells</cell_line> , showed rather low surface <protein>ICAM-1</protein> expression and <rna>ICAM-1 mRNA</rna> expression .


Southern blot hybridization showed that only two and four bands were found in ILT-mat and ATL16T ( - ) cells , respectively , whereas > 10 bands were detected in other ATL cells .

Southern blot hybridization showed that only two and four bands were found in <cell_line>ILT-mat</cell_line> and <cell_line>ATL16T ( - ) cells</cell_line> , respectively , whereas > 10 bands were detected in other <cell_line>ATL cells</cell_line> .


These results suggest that monoclonal integration of HTLV-1 provirus to the genome of T cell , especially the number of integration sites , is one of the factors for induction of ICAM-1 molecules .

These results suggest that monoclonal integration of HTLV-1 provirus to the genome of <cell_type>T cell</cell_type> , especially the number of integration sites , is one of the factors for induction of <protein>ICAM-1 molecules</protein> .


Heat-shock and cadmium chloride increase the vimentin mRNA and protein levels in U-937 human promonocytic cells .

Heat-shock and cadmium chloride increase the vimentin mRNA and protein levels in <cell_line>U-937 human promonocytic cells</cell_line> .


Heat-shock for 2 hours at 42 degrees C , or the administration for 3 hours of 100 or 150 microM cadmium chloride , inhibited the subsequent proliferation activity , induced the expression of functional differentiation markers , and caused an increase in the amount of the stress-responsive HSP70 protein in U-937 human promonocytic cells .

Heat-shock for 2 hours at 42 degrees C , or the administration for 3 hours of 100 or 150 microM cadmium chloride , inhibited the <cell_line>subsequent proliferation activity</cell_line> , induced the expression of functional <protein>differentiation markers</protein> , and caused an increase in the amount of the <protein>stress-responsive HSP70 protein</protein> in <cell_line>U-937 human promonocytic cells</cell_line> .


In addition , both heat and cadmium produced an increase in the amount of the intermediate filament protein vimentin , as determined by immunoblot and immunofluorescence assays .

In addition , both heat and cadmium produced an increase in the amount of the <protein>intermediate filament protein</protein> <protein>vimentin</protein> , as determined by immunoblot and immunofluorescence assays .


By contrast , the amounts of actin and beta-tubulin were not significantly altered .

By contrast , the amounts of <protein>actin</protein> and <protein>beta-tubulin</protein> were not significantly altered .


The amount of vimentin mRNA was also increased during recovery from stress , indicating that vimentin expression was not exclusively regulated at the protein level .

The amount of <rna>vimentin mRNA</rna> was also increased during recovery from stress , indicating that <protein>vimentin</protein> expression was not exclusively regulated at the protein level .


Although cadmium caused an early , transient stimulation of c-jun and c-fos expression and AP-1 binding activity , heat-shock failed to alter both protooncogene expression and transcription factor binding , indicating that the stress-induced vimentin increase was not the result of AP-1 -mediated transcriptional activation .

Although cadmium caused an early , transient stimulation of <dna>c-jun</dna> and <dna>c-fos</dna> expression and <protein>AP-1</protein> binding activity , heat-shock failed to alter both <dna>protooncogene</dna> expression and transcription factor binding , indicating that the stress-induced <protein>vimentin</protein> increase was not the result of <protein>AP-1</protein> -mediated transcriptional activation .


Finally , it was observed that the rate of decay of vimentin mRNA upon actinomycin D administration was decreased in heat- and cadmium-pretreated cells in comparison to untreated cells .

Finally , it was observed that the rate of decay of <rna>vimentin mRNA</rna> upon actinomycin D administration was decreased in <cell_line>heat- and cadmium-pretreated cells</cell_line> in comparison to <cell_type>untreated cells</cell_type> .


These results indicate that stress treatments cause an increase in vimentin levels in promonocytic cells , which may be explained at least in part by transcript stabilization .

These results indicate that stress treatments cause an increase in <protein>vimentin</protein> levels in <cell_type>promonocytic cells</cell_type> , which may be explained at least in part by transcript stabilization .


Ovarian and breast cytotoxic T lymphocytes can recognize peptides from the amino enhancer of split protein of the Notch complex .

Ovarian and breast <cell_type>cytotoxic T lymphocytes</cell_type> can recognize peptides from the amino enhancer of split protein of the <protein>Notch complex</protein> .


In this study we investigated recognition by ovarian tumor associated lymphocyte ( OVTAL ) , and breast tumor associated lymphocytes ( BRTAL ) , of peptides corresponding to the sequence 125-135 of the Aminoenhancer of split ( AES ) protein .

In this study we investigated recognition by <cell_type>ovarian tumor associated lymphocyte</cell_type> ( <cell_type>OVTAL</cell_type> ) , and <cell_type>breast tumor associated lymphocytes</cell_type> ( <cell_type>BRTAL</cell_type> ) , of peptides corresponding to the sequence <protein>125-135 of the Aminoenhancer of split ( AES ) protein</protein> .


Three of these peptides designated as G75 : AES1/2 ( 128-135 ) , G60 : AES1/2 ( 127-137 ) and G61 : AES1/2 ( 125-133 ) correspond to the wildtype AES sequence , while the fourth G76 : GPLTPLPV , AES1/2 ( 128-135 ) corresponds to a variant sequence of the peptide G75 with the N-terminal Leu substituted to glycine .

Three of these peptides designated as G75 : AES1/2 ( <protein>128-135</protein> ) , G60 : AES1/2 ( <protein>127-137</protein> ) and G61 : AES1/2 ( <protein>125-133</protein> ) correspond to the <dna>wildtype AES sequence</dna> , while the fourth G76 : GPLTPLPV , <protein>AES1/2 ( 128-135 )</protein> corresponds to a variant sequence of the peptide G75 with the N-terminal Leu substituted to glycine .


These sequences were chosen for study because mass-spectrometric analysis ( MS ) of a CTL active HPLC peptide fraction eluted from immunoaffinity precipitated HLA-A2 molecule , revealed : ( a ) the presence of an ion with a mass-to-charge ratio ( m/z ) of 793 which was more abundant than other ions of similar masses ; ( b ) the tentatively reconstituted sequence of the ion 793 matched the sequence of peptide G76 .

These sequences were chosen for study because mass-spectrometric analysis ( MS ) of a <cell_type>CTL</cell_type> active HPLC peptide fraction eluted from <protein>immunoaffinity precipitated HLA-A2 molecule</protein> , revealed : ( a ) the presence of an ion with a mass-to-charge ratio ( m/z ) of 793 which was more abundant than other ions of similar masses ; ( b ) the tentatively reconstituted sequence of the ion 793 matched the sequence of peptide G76 .


We found that AES peptides G75 ( 128-135 ) and G76 ( 128-135 ) ( L128G ) reconstituted CTL recognition at concentrations ranging between 200-500 nM .

We found that AES peptides G75 ( <protein>128-135</protein> ) and G76 ( <protein>128-135</protein> ) ( L128G ) reconstituted CTL recognition at concentrations ranging between 200-500 nM .


These concentrations are lower than concentrations reported to activate effector function of CTL recognizing other epithelial tumor Ag .

These concentrations are lower than concentrations reported to activate effector function of CTL recognizing other <protein>epithelial tumor Ag</protein> .


Furthermore , analysis with cloned CD8+ T cells indicated that G75 and G76 were not cross-reactive specificities , suggesting a key role for the N-terminal residues of the variant peptide in dictating specificities .

Furthermore , analysis with cloned <cell_type>CD8+ T cells</cell_type> indicated that G75 and G76 were not cross-reactive specificities , suggesting a key role for the <protein>N-terminal residues</protein> of the variant peptide in dictating specificities .


Since the AES proteins are part of a set of transcriptional repressors encoded by the Enhancer of split [ E ( spl ) ] genes , and since these repressors are activated to suppress cell differentiation in response to Notch receptors signalling , the AES peptides may represent a novel class of self-antigens that deserve further consideration as tumor Ag in epithelial cancers .

Since the <protein>AES proteins</protein> are part of a set of transcriptional repressors encoded by the <dna>Enhancer of split [ E ( spl ) ] genes</dna> , and since these repressors are activated to suppress cell differentiation in response to <protein>Notch receptors</protein> signalling , the AES peptides may represent a novel class of <protein>self-antigens</protein> that deserve further consideration as <protein>tumor Ag</protein> in epithelial cancers .


Induction of the pro-myelocytic leukaemia gene by type I and type II interferons .

Induction of the <dna>pro-myelocytic leukaemia gene</dna> by <protein>type I and type II interferons</protein> .


The physiological role of the pro-myelocytic leukaemia ( PML ) gene product is poorly defined .

The physiological role of the <protein>pro-myelocytic leukaemia ( PML ) gene product</protein> is poorly defined .


Among other functions , PML is involved in haematopoietic differentiation and in control of cell growth and tumorigenesis .

Among other functions , <dna>PML</dna> is involved in haematopoietic differentiation and in control of cell growth and tumorigenesis .


We investigated the regulation of human PML expression by interferons ( IFNs ) and IL-1 in various human haematopoietic lines ( U937 , THP1 , HL60 , NB4 ) , in human diploid fibroblasts and in human peripheral blood leukocytes .

We investigated the regulation of human <dna>PML</dna> expression by <protein>interferons</protein> ( <protein>IFNs</protein> ) and <protein>IL-1</protein> in various <cell_line>human haematopoietic lines</cell_line> ( <cell_line>U937</cell_line> , <cell_line>THP1</cell_line> , <cell_line>HL60</cell_line> , <cell_line>NB4</cell_line> ) , in <cell_type>human diploid fibroblasts</cell_type> and in <cell_type>human peripheral blood leukocytes</cell_type> .


Cytokine-induced modulation of PML expression was assessed by Northern blot analyses , flow cytometry studies and in situ immunolabelling .

Cytokine-induced modulation of <dna>PML</dna> expression was assessed by Northern blot analyses , flow cytometry studies and in situ immunolabelling .


Our data show that IFNs and IL-1 upregulate PML transcript and protein expression in a time and dose-dependent manner .

Our data show that <protein>IFNs</protein> and <protein>IL-1</protein> upregulate PML transcript and protein expression in a time and dose-dependent manner .


In situ immunolabelling revealed that upregulation of protein expression by IFN-alpha is a consequence of a marked increase in both the number and the intensity of the staining of so-called PML nuclear bodies .

In situ immunolabelling revealed that upregulation of protein expression by <protein>IFN-alpha</protein> is a consequence of a marked increase in both the number and the intensity of the staining of so-called <protein>PML nuclear bodies</protein> .


Our data suggest that stimulation of PML expression by interferons and IL-1 may account for upregulation of PML proteins observed in inflammatory tissues and in proliferative states .

Our data suggest that stimulation of <dna>PML</dna> expression by <protein>interferons</protein> and <protein>IL-1</protein> may account for upregulation of <protein>PML proteins</protein> observed in inflammatory tissues and in proliferative states .


The position of the ZEBRA activation domain does not influence its biological activity .

The position of the <protein>ZEBRA activation domain</protein> does not influence its biological activity .


Epstein-Barr virus ( EBV ) is a human herpesvirus which latently infects B lymphocytes .

Epstein-Barr virus ( EBV ) is a human herpesvirus which latently infects <cell_type>B lymphocytes</cell_type> .


EBV encodes a unique transcriptional activator , known as ZEBRA , which can disrupt viral latency in B cells and induce lytic viral replication .

EBV encodes a unique transcriptional activator , known as <protein>ZEBRA</protein> , which can disrupt viral latency in <cell_type>B cells</cell_type> and induce lytic viral replication .


Furthermore , ZEBRA has been shown to bind at the EBV origin of lytic replication , and is necessary for viral DNA replication to occur .

Furthermore , <protein>ZEBRA</protein> has been shown to bind at the EBV origin of lytic replication , and is necessary for viral DNA replication to occur .


Previously we demonstrated that heterologous activation domains can fully substitute for the ZEBRA activation domain .

Previously we demonstrated that <protein>heterologous activation domains</protein> can fully substitute for the <protein>ZEBRA activation domain</protein> .


Here we extend those results by showing that the position of the ZEBRA activation domain or a heterologous replacement domain does not influence its ability to function in the disruption of EBV latency .

Here we extend those results by showing that the position of the <protein>ZEBRA activation domain</protein> or a heterologous replacement domain does not influence its ability to function in the disruption of EBV latency .


In this study three novel clones were constructed in which the ZEBRA activation region was repositioned to the carboxy terminus of the protein .

In this study three novel clones were constructed in which the <protein>ZEBRA activation region</protein> was repositioned to the <protein>carboxy terminus</protein> of the protein .


These mutants were used to demonstrate that the ability of ZEBRA 's wild type domain to function in the complex biological process of virus activation is not compromised by altering its position within the protein .

These mutants were used to demonstrate that the ability of <protein>ZEBRA 's wild type domain</protein> to function in the complex biological process of virus activation is not compromised by altering its position within the protein .


The modulation of glucocorticoid receptor content by 3-O-methyl-D-glucose transport in human mononuclear leukocyte in obesity .

The modulation of <protein>glucocorticoid receptor</protein> content by 3-O-methyl-D-glucose transport in <cell_type>human mononuclear leukocyte</cell_type> in obesity .


Glucocorticoid receptors ( GR ) and 3-O-methyl-D glucose ( 3-O-MG ) transport were determined in mononuclear leukocytes ( MNL ) from 11 abdominal obese subjects , 10 pituitary-dependent Cushing 's syndrome ( Cushing 's disease ) and 10 healthy controls .

<protein>Glucocorticoid receptors</protein> ( <protein>GR</protein> ) and 3-O-methyl-D glucose ( 3-O-MG ) transport were determined in <cell_type>mononuclear leukocytes</cell_type> ( <cell_type>MNL</cell_type> ) from 11 abdominal obese subjects , 10 pituitary-dependent Cushing 's syndrome ( Cushing 's disease ) and 10 healthy controls .


Using a whole-cell competitive binding assay and 3H-dexamethasone as tracer , MNL of abdominal obese subjects were found to have 4855 +/- 1389 sites/cell which was significantly lower ( p < 0.05 ) than controls ( 6234 +/- 1568 sites/cell ) , although no significant difference was found in the mean serum cortisol level .

Using a whole-cell competitive binding assay and 3H-dexamethasone as tracer , <cell_type>MNL</cell_type> of abdominal obese subjects were found to have 4855 +/- 1389 sites/cell which was significantly lower ( p < 0.05 ) than controls ( 6234 +/- 1568 sites/cell ) , although no significant difference was found in the mean serum cortisol level .


Their mean Kd ( affinity ) was also significantly lower than that found in the healthy controls ( obese Kd : 2.92 +/- 0.84 nmol/l , control Kd : 4.55 +/- 0.67 nM , p < 0.05 ) .


On the other hand , the receptor characteristics in Cushing 's disease patients were within the normal range .


At the same time , 3-O-MG transport was determined in the same subjects .


In Cushing 's disease , 3-O-MG transport was within the normal range , whereas in abdominal obesity this value was significantly lower than the healthy controls ( abdominal obese : 31.90 +/- 8.20 ; control : 46.26 +/- 12.91 fmol/10 ( 6 ) cell , min , p < 0.05 ) .


We also found a positive correlation between 3-O-MG transport and GR binding capacity in abdominal subjects ( r = 0.89 , p < 0.001 ) , however we did not find such a correlation in Cushing 's disease ( r = 0.60 , p > 0.05 ) .

We also found a positive correlation between 3-O-MG transport and <protein>GR</protein> binding capacity in abdominal subjects ( r = 0.89 , p < 0.001 ) , however we did not find such a correlation in Cushing 's disease ( r = 0.60 , p > 0.05 ) .


These results indicated that , in abdominal obesity , the GR binding capacity in MNL is influenced by the changes in glucose transport .

These results indicated that , in abdominal obesity , the <protein>GR</protein> binding capacity in <cell_type>MNL</cell_type> is influenced by the changes in glucose transport .


Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma .

<protein>Interleukin-10</protein> and <dna>transforming growth factor-beta promoter polymorphisms</dna> in allergies and asthma .


Interleukin-10 ( IL-10 ) and transforming growth factor beta ( TGF-beta ) are inhibitory for B and T cells , IgE production , and mast cell proliferation , and they induce apoptosis in eosinophils .

<protein>Interleukin-10</protein> ( <protein>IL-10</protein> ) and <protein>transforming growth factor beta</protein> ( <protein>TGF-beta</protein> ) are inhibitory for <cell_type>B and T cells</cell_type> , <protein>IgE</protein> production , and mast cell proliferation , and they induce apoptosis in <cell_type>eosinophils</cell_type> .


These cytokines are therefore candidate genes which could contribute to the development of asthma or allergies .

These <protein>cytokines</protein> are therefore candidate genes which could contribute to the development of asthma or allergies .


We investigated the hypothesis that polymorphic nucleotides within the IL-10 and TGF-beta gene promoters would link to the expression of allergies and asthma .

We investigated the hypothesis that polymorphic nucleotides within the <dna>IL-10 and TGF-beta gene promoters</dna> would link to the expression of allergies and asthma .


DNA taken from families with an asthmatic proband was examined for base exchanges by single-stranded conformational polymorphism ( SSCP ) .


We demonstrated the presence of a polymorphism in the promoter region of the IL-10 gene and four in the TGF-beta gene promoters ( 3 in TGF-beta1 and 1 in TGF-beta2 ) .

We demonstrated the presence of a polymorphism in the <dna>promoter region</dna> of the <dna>IL-10 gene</dna> and four in the <dna>TGF-beta gene promoters</dna> ( 3 in <dna>TGF-beta1</dna> and 1 in <dna>TGF-beta2</dna> ) .


The IL-10 gene polymorphism was a C-to-A exchange 571 base pairs upstream from the translation start site and was present between consensus binding sequences for Sp1 and elevated total serum .

The <protein>IL-10</protein> gene polymorphism was a C-to-A exchange <dna>571 base pairs upstream</dna> from the <dna>translation start site</dna> and was present between <dna>consensus binding sequences</dna> for <protein>Sp1</protein> and elevated total serum .


This polymorphism was associated with elevated total serum IgE in subjects heterozygotic or homozygotic for this base exchange ( p < 0.009 ) .

This polymorphism was associated with elevated <protein>total serum IgE</protein> in subjects heterozygotic or homozygotic for this base exchange ( p < 0.009 ) .


The base exchange at -509 ( from the transcription initiation site ) in the TGF-beta promoter also linked to elevated total IgE ( p < 0.01 ) .

The base exchange at -509 ( from the transcription initiation site ) in the <dna>TGF-beta promoter</dna> also linked to elevated total <protein>IgE</protein> ( p < 0.01 ) .


This polymorphism represented a C-to-T base exchange which induced a YY1 consensus sequence and is present in a region of the promoter associated with negative transcription regulation .

This polymorphism represented a C-to-T base exchange which induced a <dna>YY1 consensus sequence</dna> and is present in a region of the promoter associated with negative transcription regulation .


Tpl-2 induces IL-2 expression in T-cell lines by triggering multiple signaling pathways that activate NFAT and NF-kappaB .

<protein>Tpl-2</protein> induces <protein>IL-2</protein> expression in <cell_line>T-cell lines</cell_line> by triggering multiple signaling pathways that activate <protein>NFAT</protein> and <protein>NF-kappaB</protein> .


The Tpl-2 kinase activates the nuclear factor of activated T cells ( NFAT ) and induces IL-2 expression in T-cell lines .

The <protein>Tpl-2 kinase</protein> activates the <protein>nuclear factor of activated T cells</protein> ( <protein>NFAT</protein> ) and induces <protein>IL-2</protein> expression in <cell_line>T-cell lines</cell_line> .


Here we show that the activation of the IL-2 promoter by Tpl-2 is inhibited by mutant signaling molecules that inhibit the mitogen-activated protein kinase ( MAPK ) or the calcineurin /NFAT pathways and is promoted by combinations of signaling molecules that activate these pathways .

Here we show that the activation of the <dna>IL-2 promoter</dna> by <protein>Tpl-2</protein> is inhibited by <protein>mutant signaling molecules</protein> that inhibit the <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) or the <protein>calcineurin</protein> <protein>/NFAT</protein> pathways and is promoted by combinations of <protein>signaling molecules</protein> that activate these pathways .


We , therefore , conclude that signals generated by the convergence of the MAPK and the calcineurin /NFAT pathway are necessary and sufficient for the activation of the IL-2 promoter by Tpl-2 .

We , therefore , conclude that signals generated by the convergence of the <protein>MAPK</protein> and the <protein>calcineurin</protein> <protein>/NFAT</protein> pathway are necessary and sufficient for the activation of the <dna>IL-2 promoter</dna> by <protein>Tpl-2</protein> .


The activation of both the IL-2 promoter and an NFAT-driven minimal promoter were shown to depend on signals transduced by Raf1 .

The activation of both the <dna>IL-2 promoter</dna> and an <dna>NFAT-driven minimal promoter</dna> were shown to depend on signals transduced by <protein>Raf1</protein> .


However , it was only the IL-2 promoter whose activation by Tpl-2 was fully blocked by the dominant negative mutant MEK1S218/222A and the MEK1/MEK2 inhibitor PD098059 .

However , it was only the <dna>IL-2 promoter</dna> whose activation by <protein>Tpl-2</protein> was fully blocked by the <protein>dominant negative mutant MEK1S218/222A</protein> and the MEK1/MEK2 inhibitor PD098059 .


Since the activation of NFAT is MAPK -dependent these findings suggested that the activation of MAPK by Tpl-2 is either independent or only partially dependent on MEK1 and MEK2 .

Since the activation of <protein>NFAT</protein> is <protein>MAPK</protein> -dependent these findings suggested that the activation of <protein>MAPK</protein> by <protein>Tpl-2</protein> is either independent or only partially dependent on <protein>MEK1</protein> and <protein>MEK2</protein> .


In addition , they suggested that the activation of the IL-2 promoter is under the control of not only NFAT but also a second factor whose activation is MEK -dependent .

In addition , they suggested that the activation of the <dna>IL-2 promoter</dna> is under the control of not only <protein>NFAT</protein> but also a second factor whose activation is <protein>MEK</protein> -dependent .


Experiments in COS-1 and EL-4 cells confirmed both hypotheses and revealed that the second factor activated by Tpl-2 is NF-kappaB .

Experiments in <cell_line>COS-1</cell_line> and <cell_line>EL-4 cells</cell_line> confirmed both hypotheses and revealed that the second factor activated by <protein>Tpl-2</protein> is <protein>NF-kappaB</protein> .


While the activation of the IL-2 promoter and an NFAT-driven minimal promoter by Tpl-2 was fully blocked by the dominant negative mutant NFAT delta418 , it was only partially blocked by the calcineurin inhibitor cyclosporin A suggesting that the Tpl-2 -mediated NFAT activation is under the control of a combination of calcineurin-dependent and independent pathways .

While the activation of the <dna>IL-2 promoter</dna> and an <dna>NFAT-driven minimal promoter</dna> by <protein>Tpl-2</protein> was fully blocked by the <protein>dominant negative mutant</protein> <protein>NFAT delta418</protein> , it was only partially blocked by the <protein>calcineurin</protein> inhibitor cyclosporin A suggesting that the <protein>Tpl-2</protein> -mediated <protein>NFAT</protein> activation is under the control of a combination of calcineurin-dependent and independent pathways .


Both pathways were fully blocked by Bcl-2 or Bcl-X ( L ) .

Both pathways were fully blocked by <protein>Bcl-2</protein> or <protein>Bcl-X ( L )</protein> .


Differential activation of functionally distinct STAT5 proteins by IL-5 and GM-CSF during eosinophil and neutrophil differentiation from human CD34+ hematopoietic stem cells .

Differential activation of functionally distinct <protein>STAT5 proteins</protein> by <protein>IL-5</protein> and <protein>GM-CSF</protein> during eosinophil and neutrophil differentiation from <cell_line>human CD34+ hematopoietic stem cells</cell_line> .


Interleukin-5 ( IL-5 ) and granulocyte macrophage-colony stimulating factor ( GM-CSF ) are important cytokines for the proliferation , differentiation , and activation of myeloid lineages .

<protein>Interleukin-5</protein> ( <protein>IL-5</protein> ) and <protein>granulocyte macrophage-colony stimulating factor</protein> ( <protein>GM-CSF</protein> ) are important <protein>cytokines</protein> for the proliferation , differentiation , and activation of <cell_type>myeloid lineages</cell_type> .


The JAK /STAT pathway is one of the signaling pathways implicated in mediating biological responses induced by these cytokines .

The <protein>JAK</protein> <protein>/STAT</protein> pathway is one of the signaling pathways implicated in mediating biological responses induced by these <protein>cytokines</protein> .


Previous studies have demonstrated that these cytokines predominantly activate an 80 kDa STAT5 isoform in mature granulocytes .

Previous studies have demonstrated that these <protein>cytokines</protein> predominantly activate an <protein>80 kDa STAT5 isoform</protein> in mature granulocytes .


To better understand the role of STAT proteins during growth and differentiation of granulocytes , we evaluated differentiation of human CD34+ hematopoietic stem cells ex vivo toward eosinophils and neutrophils .

To better understand the role of STAT proteins during growth and differentiation of granulocytes , we evaluated differentiation of <cell_line>human CD34+ hematopoietic stem cells</cell_line> ex vivo toward <cell_type>eosinophils</cell_type> and neutrophils .


Bandshift experiments showed that in an early stage of both differentiation pathways ( 14 days ) , the 94 kDa STAT5B protein was activated by both IL-5 ( eosinophil lineage ) and GM-CSF ( neutrophil lineage ) .

Bandshift experiments showed that in an early stage of both differentiation pathways ( 14 days ) , the 94 kDa <protein>STAT5B protein</protein> was activated by both <protein>IL-5</protein> ( <cell_type>eosinophil lineage</cell_type> ) and <protein>GM-CSF</protein> ( <cell_type>neutrophil lineage</cell_type> ) .


However , during maturation of both lineages ( days 21 and 28 ) , increased expression of a functionally distinct 80 kDa STAT5 isoform was observed , resulting in heterodimer DNA-binding complexes containing both the 94 and 80 kDa STAT5 proteins .

However , during maturation of both lineages ( days 21 and 28 ) , increased expression of a functionally distinct <protein>80 kDa STAT5 isoform</protein> was observed , resulting in <protein>heterodimer DNA-binding complexes</protein> containing both the 94 and 80 kDa <protein>STAT5 proteins</protein> .


The finding that functionally distinct isoforms of STAT5 are activated during the early and late differentiation stages of granulocytes suggests that they might be involved in regulating different biological functions in these cells .

The finding that functionally distinct isoforms of <protein>STAT5</protein> are activated during the early and late differentiation stages of granulocytes suggests that they might be involved in regulating different biological functions in these cells .


The T-cell oncogenic protein HOX11 activates Aldh1 expression in NIH 3T3 cells but represses its expression in mouse spleen development .

The <protein>T-cell oncogenic protein HOX11</protein> activates <protein>Aldh1</protein> expression in <cell_line>NIH 3T3 cells</cell_line> but represses its expression in mouse spleen development .


Hox11 is a homeobox gene essential for spleen formation in mice , since atrophy of the anlage of a developing spleen occurs in early embryonic development in Hox11 null mice .

<dna>Hox11</dna> is a <dna>homeobox gene</dna> essential for spleen formation in mice , since atrophy of the anlage of a developing spleen occurs in early embryonic development in Hox11 null mice .


HOX11 is also expressed in a subset of T-cell acute leukemias after specific chromosomal translocations .

<protein>HOX11</protein> is also expressed in a subset of T-cell acute leukemias after specific chromosomal translocations .


Since the protein has a homeodomain and can activate transcription , it probably exerts at least some of its effects in vivo by regulation of target genes .

Since the protein has a <dna>homeodomain</dna> and can activate transcription , it probably exerts at least some of its effects in vivo by regulation of <dna>target genes</dna> .


Representational difference analysis has been used to isolate cDNA clones corresponding to mRNA species activated following stable expression of HOX11 in NIH 3T3 cells .

Representational difference analysis has been used to isolate <dna>cDNA clones</dna> corresponding to <rna>mRNA species</rna> activated following stable expression of <protein>HOX11</protein> in <cell_line>NIH 3T3 cells</cell_line> .


The gene encoding the retinoic acid-synthesizing enzyme aldehyde dehydrogenase 1 ( Aldh1 ) , initially called Hdg-1 , was found to be ectopically activated by HOX11 in this system .

The gene encoding the <protein>retinoic acid-synthesizing enzyme</protein> <protein>aldehyde dehydrogenase 1</protein> ( <protein>Aldh1</protein> ) , initially called <protein>Hdg-1</protein> , was found to be ectopically activated by <protein>HOX11</protein> in this system .


Study of Aldh1 gene expression during spleen development showed that the presence of Aldh1 mRNA inversely correlated with Hox11 .

Study of <protein>Aldh1</protein> gene expression during spleen development showed that the presence of <rna>Aldh1 mRNA</rna> inversely correlated with <protein>Hox11</protein> .


Hox11 null mouse embryos have elevated Aldh1 mRNA in spleen primordia prior to atrophy , while Aldh1 seems to be repressed by Hox11 during organogenesis of the spleens of wild-type mice .

<protein>Hox11</protein> null mouse embryos have elevated <rna>Aldh1 mRNA</rna> in spleen primordia prior to atrophy , while <protein>Aldh1</protein> seems to be repressed by <protein>Hox11</protein> during organogenesis of the spleens of wild-type mice .


This result suggests that expression of Aldh1 protein is negatively regulated by Hox11 and that abnormal expression of Aldh1 in Hox11 null mice may cause loss of splenic precursor cells by aberrant retinoic acid metabolism

This result suggests that expression of <protein>Aldh1 protein</protein> is negatively regulated by <protein>Hox11</protein> and that abnormal expression of <protein>Aldh1</protein> in <protein>Hox11</protein> null mice may cause loss of <cell_type>splenic precursor cells</cell_type> by aberrant retinoic acid metabolism


Role of the X2 box in activated transcription from the DRA promoter in B cells .

Role of the <dna>X2 box</dna> in activated transcription from the <dna>DRA promoter</dna> in <cell_type>B cells</cell_type> .


We investigated the function of the evolutionary conserved X2 box in the promoter of the HLA-DRA gene from the human major histocompatibility complex ( MHC ) in resting and activated B cells .

We investigated the function of the evolutionary conserved <dna>X2 box</dna> in the <dna>promoter</dna> of the <dna>HLA-DRA gene</dna> from the <protein>human major histocompatibility complex</protein> ( <protein>MHC</protein> ) in resting and activated <cell_type>B cells</cell_type> .


NF-X2 , which contains members of the AP-1/ATF/CREB families of transcription factors , interacts with the X2 box ( 5'-TGCGTCA-3 ' ) from positions -97 to -91 in the DRA promoter .

<dna>NF-X2</dna> , which contains members of the <protein>AP-1/ATF/CREB families</protein> of <protein>transcription factors</protein> , interacts with the <dna>X2 box</dna> ( 5'-TGCGTCA-3 ' ) from positions -97 to -91 in the <dna>DRA promoter</dna> .


In resting Raji cells , little to no binding to the X2 box was observed .

In resting <cell_line>Raji cells</cell_line> , little to no binding to the <dna>X2 box</dna> was observed .


In sharp contrast , in B cells treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate ( TPA ) , strong interactions between the X2 box and NF-X2 containing c-Fos were observed .

In sharp contrast , in <cell_type>B cells</cell_type> treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate ( TPA ) , strong interactions between the <dna>X2 box</dna> and <dna>NF-X2</dna> containing <protein>c-Fos</protein> were observed .


As determined by transient expression and RNA analyses , the activation of protein kinase C ( PKC ) also increased rates of transcription from the wild-type DRA promoter but not from a DRA promoter bearing clustered point mutations in the X2 box .

As determined by transient expression and RNA analyses , the activation of protein kinase C ( PKC ) also increased rates of transcription from the wild-type <dna>DRA promoter</dna> but not from a <dna>DRA promoter</dna> bearing clustered point mutations in the <dna>X2 box</dna> .


Since the co-expression with a dominant negative c-Fos abolished the responsiveness to TPA , we conclude that activated transcription of the DRA gene depends on interactions between the X2 box and NF-X2 , which contains c-Fos .

Since the co-expression with a dominant negative <protein>c-Fos</protein> abolished the responsiveness to TPA , we conclude that activated transcription of the <dna>DRA gene</dna> depends on interactions between the <dna>X2 box</dna> and <dna>NF-X2</dna> , which contains <protein>c-Fos</protein> .


Thymocytes control the CD4 gene differently from mature T lymphocytes .

Thymocytes control the <dna>CD4 gene</dna> differently from <cell_type>mature T lymphocytes</cell_type> .


We analyzed the activity of the enhancer , the promoter and the silencer of the human CD4 gene during T cell development using transgenic mice .

We analyzed the activity of the <dna>enhancer</dna> , the <dna>promoter</dna> and the <dna>silencer</dna> of the <dna>human CD4 gene</dna> during T cell development using transgenic mice .


Immunofluorescence studies on thymic populations of mice carrying transgenes in various combinations of these regulatory DNA elements revealed that thymocytes control the CD4 gene in a different manner than mature peripheral T lymphocytes .

Immunofluorescence studies on <cell_type>thymic populations</cell_type> of mice carrying transgenes in various combinations of these <dna>regulatory DNA elements</dna> revealed that <cell_type>thymocytes</cell_type> control the <dna>CD4 gene</dna> in a different manner than mature <cell_type>peripheral T lymphocytes</cell_type> .


The 5'-positive regulatory unit , consisting of the promoter and the 5 ' enhancer , is already active at the CD4 - CD8 -double-negative ( DN ) stage of development .

The <dna>5'-positive regulatory unit</dna> , consisting of the <dna>promoter</dna> and the <dna>5 ' enhancer</dna> , is already active at the <protein>CD4</protein> - <protein>CD8</protein> -double-negative ( DN ) stage of development .


However , its activity becomes lower in the double-positive and a fraction of the CD4+ CD8int/- cell population , indicating that an additional enhancer , located in either the first or the third intron of the CD4 gene , is required for CD4 gene expression in this population .

However , its activity becomes lower in the double-positive and a fraction of the <cell_type>CD4+ CD8int/- cell population</cell_type> , indicating that an additional enhancer , located in either the <dna>first or the third intron</dna> of the <dna>CD4 gene</dna> , is required for <dna>CD4 gene</dna> expression in this population .


The other studied regulatory element is the minimal CD4 silencer which inhibits CD4 gene expression in peripheral CD8 T lymphocytes .

The other studied <dna>regulatory element</dna> is the <dna>minimal CD4 silencer</dna> which inhibits <dna>CD4 gene</dna> expression in <cell_type>peripheral CD8 T lymphocytes</cell_type> .


This silencer is inactive in the most immature DN thymocytes , which probably use a distinct silencer mechanism to down-regulate CD4 gene expression .

This silencer is inactive in the most <cell_type>immature DN thymocytes</cell_type> , which probably use a distinct silencer mechanism to down-regulate <dna>CD4 gene</dna> expression .


Unexpectedly , the CD4 silencer is also active in CD4+ CD8int/- cells of the thymus , implying that an anti-silencer may be required to resume CD4 expression in this cell population .

Unexpectedly , the <dna>CD4 silencer</dna> is also active in <cell_type>CD4+ CD8int/- cells</cell_type> of the thymus , implying that an anti-silencer may be required to resume <protein>CD4</protein> expression in this cell population .


Altogether , the CD4 gene is regulated by several positive and negative regulatory mechanisms which come into play in a developmentally coordinated manner .

Altogether , the <dna>CD4 gene</dna> is regulated by several positive and negative regulatory mechanisms which come into play in a developmentally coordinated manner .


[ Induction of apoptosis in lymphocytes by glucocorticoids : between physiology and pharmacology ]

[ Induction of apoptosis in <cell_type>lymphocytes</cell_type> by glucocorticoids : between physiology and pharmacology ]


Glucocorticoids are physiological molecules that are also extensively used in clinics as anti-inflammatory , immunosuppressive or anti-tumoral agents .


Glucocorticoids can induce apoptosis on normal lymphoid cells and play a key role in the physiology of thymic selection .

Glucocorticoids can induce apoptosis on <cell_type>normal lymphoid cells</cell_type> and play a key role in the physiology of thymic selection .


In clinics these molecules are also used for their potencies in inducing apoptosis of malignant lymphoid cells .

In clinics these molecules are also used for their potencies in inducing apoptosis of <cell_type>malignant lymphoid cells</cell_type> .


Glucocorticoids are mediating their effects after binding to an intracellular receptor belonging to the steroid receptor superfamily : the glucocorticoid receptor ( GR ) .

Glucocorticoids are mediating their effects after binding to an <protein>intracellular receptor</protein> belonging to the <protein>steroid receptor superfamily</protein> : the <protein>glucocorticoid receptor</protein> ( <protein>GR</protein> ) .


Once activated , the GR , can mediate his effects through direct binding on the DNA or via protein/protein interactions with transcription factors .

Once activated , the <protein>GR</protein> , can mediate his effects through direct binding on the DNA or via protein/protein interactions with <protein>transcription factors</protein> .


Depending on the type of lymphocytes , the mechanism of apoptosis induced by glucocorticoids fall roughly in two categories : induction of `` death genes '' by the activated GR ( I kappa B , c-jun ) or repression of survival factors ( AP-1 , c-Myc ) .

Depending on the type of <cell_type>lymphocytes</cell_type> , the mechanism of apoptosis induced by glucocorticoids fall roughly in two categories : induction of `` death genes '' by the activated <protein>GR</protein> ( <protein>I kappa B</protein> , <protein>c-jun</protein> ) or repression of <protein>survival factors</protein> ( <protein>AP-1</protein> , <protein>c-Myc</protein> ) .


In the case of thymic selection the mechanism is more subtle depending on the mutual repression of Nur77 and GR .

In the case of thymic selection the mechanism is more subtle depending on the mutual repression of <protein>Nur77</protein> and <protein>GR</protein> .


Direct suppression of Stat1 function during adenoviral infection .

Direct suppression of <protein>Stat1</protein> function during adenoviral infection .


The action of adenoviral E1A oncoprotein on host immune-response genes has been attributed to interaction with p300/CBP-type transcriptional coactivators in competition with endogenous transcription factors such as signal transducer and activator of transcription ( STAT ) proteins .

The action of <protein>adenoviral E1A oncoprotein</protein> on <dna>host immune-response genes</dna> has been attributed to interaction with <protein>p300/CBP-type transcriptional coactivators</protein> in competition with <protein>endogenous transcription factors</protein> such as <protein>signal transducer and activator of transcription ( STAT ) proteins</protein> .


However , we show that mutant forms of E1A that no longer bind p300/CBP can still interact directly with Stat1 ( via E1A N-terminal and Stat1 C-terminal residues ) and block IFNgamma-driven , Stat1 -dependent gene activation and consequent function during early-phase infection in the natural host cell .

However , we show that mutant forms of <protein>E1A</protein> that no longer bind <protein>p300/CBP</protein> can still interact directly with <protein>Stat1</protein> ( via <protein>E1A N-terminal and Stat1 C-terminal residues</protein> ) and block IFNgamma-driven , <protein>Stat1</protein> -dependent gene activation and consequent function during early-phase infection in the <cell_type>natural host cell</cell_type> .


The results provide a distinct and more specific mechanism for E1A -mediated immune suppression and an alternative model of IFNgamma -driven enhanceosome formation that may allow for other adaptors ( in addition to p300/CBP ) to link Stat1 to the basal transcription complex .

The results provide a distinct and more specific mechanism for <protein>E1A</protein> -mediated immune suppression and an alternative model of <protein>IFNgamma</protein> -driven enhanceosome formation that may allow for other adaptors ( in addition to <protein>p300/CBP</protein> ) to link <protein>Stat1</protein> to the <protein>basal transcription complex</protein> .


Effect of environmental estrogens on IL-1beta promoter activity in a macrophage cell line .

Effect of environmental estrogens on <dna>IL-1beta promoter</dna> activity in a <cell_line>macrophage cell line</cell_line> .


Environmental estrogens or estrogen disrupters have recently received a great deal of attention because of their potential health impact on reproductive tissues .


Few , if any , studies have been made on the impact of these compounds on the immune system .


We sought to determine the activities of various environmental estrogens on the modulation of the interleukin-1beta ( IL-1beta ) gene in a model monocytic cell line , hER + IL-1beta-CAT+ .

We sought to determine the activities of various environmental estrogens on the modulation of the <dna>interleukin-1beta ( IL-1beta ) gene</dna> in a <cell_line>model monocytic cell line</cell_line> , <cell_line>hER + IL-1beta-CAT+</cell_line> .


This cell line stably transfected with the human estrogen receptor , and an IL-1beta promoter construct fused to the CAT reporter gene allows us to monitor the effect of estrogenic compounds on IL-1beta promoter activity .

This cell line stably transfected with the <protein>human estrogen receptor</protein> , and an <dna>IL-1beta promoter</dna> construct fused to the <dna>CAT reporter gene</dna> allows us to monitor the effect of estrogenic compounds on <dna>IL-1beta promoter</dna> activity .


17beta-estradiol ( E2 ) markedly enhanced lipopolysaccharide - ( LPS ) induced IL-1beta promoter -driven CAT activity in a dose-dependent manner .

17beta-estradiol ( E2 ) markedly enhanced lipopolysaccharide - ( LPS ) induced <dna>IL-1beta promoter</dna> -driven <protein>CAT</protein> activity in a dose-dependent manner .


The mycotoxins alpha-zearalenol and zearalenone both exhibited full agonist activity , but at lower potencies , with EC50 values of 1.8 and 54 nM , respectively , compared with E2 at 0.5 nM .


In addition , genistein was a very low-potency agonist , having an EC50 of 1.5 microM .


Similar to the E2 response , the slope factors for alpha-zearalenol , zearalenone , and genistein were close to 3.0 , suggesting positive cooperativity in the estrogenic response .


The activity of the mycotoxins appeared to be mediated through the estrogen receptor , since both the antiestrogens H1285 and ICI 182 , 780 effectively inhibited their agonist activity in a dose-dependent manner .


Representative environmental estrogenic compounds both from plant and industrial sources were also tested .


Unlike the mycoestrogens , none of the compounds , with the exception of genistein , synergized with LPS to enhance IL-1beta promoter activity .

Unlike the mycoestrogens , none of the compounds , with the exception of genistein , synergized with LPS to enhance <dna>IL-1beta promoter</dna> activity .


When tested for antiestrogenic activity , the industrial compound 4-octylphenol was able to antagonize the response to E2 ; however , the response was three orders of magnitude less potent than H 1285 .


Naringenin , a plant flavonoid , showed little or no ability to antagonize the response to E2 .


Overall , the results show that some environmental estrogens that display agonist activity in reproductive tissue also have an effect on IL-1 gene expression in hemopoietic-derived tissue .

Overall , the results show that some environmental estrogens that display agonist activity in reproductive tissue also have an effect on <dna>IL-1 gene</dna> expression in hemopoietic-derived tissue .


Isolation and utilization of human dendritic cells from peripheral blood to assay an in vitro primary immune response to varicella-zoster virus peptides .

Isolation and utilization of <cell_type>human dendritic cells</cell_type> from peripheral blood to assay an in vitro primary immune response to varicella-zoster virus peptides .


A human dendritic cell-based assay used to monitor a T cell proliferation response to viral peptides in vitro is described .


Dendritic cells and autologous CD4+ T cells were isolated from peripheral blood by a series of density-gradient centrifugations or magnetic bead separations ( or both ) .

<cell_type>Dendritic cells</cell_type> and <cell_type>autologous CD4+ T cells</cell_type> were isolated from peripheral blood by a series of density-gradient centrifugations or magnetic bead separations ( or both ) .


Peptides corresponding to residues of the immediate early protein , IE62 , of varicella-zoster virus ( VZV ) were used as stimulating antigens , and persons with no history of varicella and no humoral or cellular immunity to VZV served as naive donors for the assays .

Peptides corresponding to residues of the <protein>immediate early protein</protein> , <protein>IE62</protein> , of varicella-zoster virus ( VZV ) were used as <protein>stimulating antigens</protein> , and persons with no history of varicella and no humoral or cellular immunity to VZV served as naive donors for the assays .


Three VZV-susceptible donors were tested , and all demonstrated an in vitro response to multiple VZV peptides .


This assay has potential as a screen to establish the immunogenicity of viral antigens in vitro using T cells from naive donors .

This assay has potential as a screen to establish the immunogenicity of viral antigens in vitro using <cell_type>T cells</cell_type> from naive donors .


Xenogeneic human serum promotes leukocyte adhesion to porcine endothelium under flow conditions , possibly through the activation of the transcription factor NF-kappa B .

Xenogeneic human serum promotes leukocyte adhesion to porcine endothelium under flow conditions , possibly through the activation of the <protein>transcription factor NF-kappa B</protein> .


Endothelial cell activation and leukocyte infiltration are a consistent feature of discordant xenograft rejection .


Here we evaluated whether xenogeneic serum , as a source of xenoreactive natural antibodies and complement , induced endothelial cell activation with consequent leukocyte adhesion under flow conditions .

Here we evaluated whether xenogeneic serum , as a source of <protein>xenoreactive natural antibodies</protein> and complement , induced endothelial cell activation with consequent leukocyte adhesion under flow conditions .


Porcine aortic endothelial cells ( PAEC ) were incubated for 1 hr 30 min or 5 hr with 10 % homologous porcine serum ( control ) or 10 % xenogeneic human serum and then perfused with total human leukocytes in a parallel plate flow chamber under laminar flow ( 1.5 dynes/cm2 ) .

<cell_line>Porcine aortic endothelial cells</cell_line> ( <cell_line>PAEC</cell_line> ) were incubated for 1 hr 30 min or 5 hr with 10 % homologous porcine serum ( control ) or 10 % xenogeneic human serum and then perfused with total <cell_type>human leukocytes</cell_type> in a parallel plate flow chamber under laminar flow ( 1.5 dynes/cm2 ) .


Adherent cells were counted by digital image analysis .


Xenogeneic human serum significantly ( P < 0.01 ) increased the number of adherent leukocytes as compared with porcine serum .

Xenogeneic human serum significantly ( P < 0.01 ) increased the number of <cell_type>adherent leukocytes</cell_type> as compared with porcine serum .


A similar adhesive response was elicited by TNF alpha ( 100 U/ml ) , one of the most potent inducers of endothelial cell adhesive properties , here used as positive control .

A similar adhesive response was elicited by TNF alpha ( 100 U/ml ) , one of the most potent inducers of <cell_type>endothelial cell</cell_type> adhesive properties , here used as positive control .


In order to elucidate possible mechanisms underlying endothelial cell activation by xenogeneic serum , we focussed on transcription factor NF-kappa B , a central regulator for the induction of different genes , including adhesive molecules and chemoattractants .

In order to elucidate possible mechanisms underlying <cell_type>endothelial cell</cell_type> activation by xenogeneic serum , we focussed on <protein>transcription factor NF-kappa B</protein> , a central regulator for the induction of different genes , including <protein>adhesive molecules</protein> and <protein>chemoattractants</protein> .


By confocal fluorescence microscopy , we observed a positive staining for NF-kappa B ( p65 subunit ) in the nuclei of PAEC exposed for 1 hr 30 min to human serum , which indicated NF-kappa B activation in this setting .

By confocal fluorescence microscopy , we observed a positive staining for <protein>NF-kappa B</protein> ( <protein>p65 subunit</protein> ) in the nuclei of <cell_line>PAEC</cell_line> exposed for 1 hr 30 min to human serum , which indicated <protein>NF-kappa B</protein> activation in this setting .


At variance , in PAEC incubated with the homologous serum , NF-kappa B was strictly localized in the cell cytoplasm .

At variance , in <cell_line>PAEC</cell_line> incubated with the homologous serum , <protein>NF-kappa B</protein> was strictly localized in the cell cytoplasm .


Treatment of PAEC exposed to xenogeneic serum with the NF-kappa B inhibitors pyrrolidinedithiocarbamate ( PDTC , 25 microM ) and tosyl-phechloromethylketone ( TPCK , 25 microM ) significantly ( P < 0.01 ) reduced leukocyte adhesion in respect to PAEC treated with human serum alone .

Treatment of <cell_line>PAEC</cell_line> exposed to xenogeneic serum with the <protein>NF-kappa B</protein> inhibitors pyrrolidinedithiocarbamate ( PDTC , 25 microM ) and tosyl-phechloromethylketone ( TPCK , 25 microM ) significantly ( P < 0.01 ) reduced leukocyte adhesion in respect to <cell_line>PAEC</cell_line> treated with human serum alone .


Findings that xenogeneic serum promotes leukocyte-endothelium interaction possibly through NF-kappa B activation might be relevant for designing future therapeutic strategies aimed at prolonging xenograft survival .

Findings that xenogeneic serum promotes leukocyte-endothelium interaction possibly through <protein>NF-kappa B</protein> activation might be relevant for designing future therapeutic strategies aimed at prolonging xenograft survival .


Anaphylatoxins C5a and C3a induce nuclear factor kappaB activation in human peripheral blood monocytes .

<protein>Anaphylatoxins</protein> <protein>C5a</protein> and <protein>C3a</protein> induce <protein>nuclear factor kappaB</protein> activation in <cell_type>human peripheral blood monocytes</cell_type> .


The anaphylatoxins C5a and C3a are involved in the regulation of cytokine production .

The <protein>anaphylatoxins</protein> <protein>C5a</protein> and <protein>C3a</protein> are involved in the regulation of cytokine production .


In this study the capability of C5a and C3a to induce transcription factor activation was examined .

In this study the capability of <protein>C5a</protein> and <protein>C3a</protein> to induce transcription factor activation was examined .


C5a and C3a stimulation of human peripheral blood monocytes resulted in nuclear expression of a DNA binding activity with specificity to the kappaB sequence .

<protein>C5a</protein> and <protein>C3a</protein> stimulation of <cell_type>human peripheral blood monocytes</cell_type> resulted in nuclear expression of a DNA binding activity with specificity to the <dna>kappaB sequence</dna> .


The p50 and p65 proteins , constituents of the prototypic nuclear factor kappaB , were identified as components of the DNA-protein complexes by anti-peptide antibodies in gel supershift assays .

The <protein>p50 and p65 proteins</protein> , constituents of the prototypic <protein>nuclear factor kappaB</protein> , were identified as components of the DNA-protein complexes by <protein>anti-peptide antibodies</protein> in gel supershift assays .


C5a induced kappaB binding activity was detected 15 min after agonist stimulation , peaked at 30-40 min , and remained detectable at 2 h .

<protein>C5a</protein> induced <protein>kappaB</protein> binding activity was detected 15 min after agonist stimulation , peaked at 30-40 min , and remained detectable at 2 h .


Binding to kappaB sequence was accompanied by an initial decrease and subsequent increase in the cytoplasmic IkappaBalpha levels , as detected by Western blotting using an anti-IkappaBalpha antibody .

Binding to <dna>kappaB sequence</dna> was accompanied by an initial decrease and subsequent increase in the cytoplasmic <protein>IkappaBalpha</protein> levels , as detected by Western blotting using an <protein>anti-IkappaBalpha antibody</protein> .


Pertussis toxin treatment markedly decreased kappaB binding activities induced by both C5a and C3a , whereas cholera toxin displayed no inhibitory effect .

Pertussis toxin treatment markedly decreased <protein>kappaB</protein> binding activities induced by both <protein>C5a</protein> and <protein>C3a</protein> , whereas <protein>cholera toxin</protein> displayed no inhibitory effect .


Neither of the two toxins affected kappaB binding activity induced by TNFalpha in the same cells .

Neither of the two toxins affected <protein>kappaB</protein> binding activity induced by <protein>TNFalpha</protein> in the same cells .


These results imply a potential role of the anaphylatoxins C5a and C3a in regulating leukocytes gene expression through G protein-coupled transcription factor activation .

These results imply a potential role of the <protein>anaphylatoxins</protein> <protein>C5a</protein> and <protein>C3a</protein> in regulating leukocytes gene expression through G protein-coupled transcription factor activation .


Thrombopoietin and its receptor .

<protein>Thrombopoietin</protein> and its receptor .


Thrombopoietin ( TPO ) , the primary physiological regulator of platelet production , was initially thought to be a lineage-specific factor acting predominantly on megakaryocytopoiesis .

<protein>Thrombopoietin</protein> ( <protein>TPO</protein> ) , the primary physiological regulator of platelet production , was initially thought to be a lineage-specific factor acting predominantly on megakaryocytopoiesis .


Detailed studies establish that this cytokine mediates biological effects on a broad spectrum of hematopoietic progenitor cells , including stem cells .

Detailed studies establish that this cytokine mediates biological effects on a broad spectrum of <cell_type>hematopoietic progenitor cells</cell_type> , including <cell_type>stem cells</cell_type> .


TPO is a hormone constitutively produced mainly by the liver and kidney .

<protein>TPO</protein> is a hormone constitutively produced mainly by the liver and kidney .


Plasma TPO levels are regulated by the platelet and megakaryocyte mass through Mpl receptor binding , internalization and degradation .

Plasma <protein>TPO</protein> levels are regulated by the platelet and megakaryocyte mass through <protein>Mpl receptor</protein> binding , internalization and degradation .


The Mpl receptor is a member of the hematopoietin receptor superfamily lacking intrinsic kinase activity .

The <protein>Mpl receptor</protein> is a member of the <protein>hematopoietin receptor superfamily</protein> lacking intrinsic kinase activity .


Upon ligand-induced Mpl homodimerization , the major signaling events for proliferation are mediated through the JAK2 /STAT5 pathway , while differentiation might occur through a prolonged activation of the MAPK pathway .

Upon ligand-induced Mpl homodimerization , the major signaling events for proliferation are mediated through the <protein>JAK2</protein> <protein>/STAT5</protein> pathway , while differentiation might occur through a prolonged activation of the <protein>MAPK</protein> pathway .


Preclinical and clinical studies demonstrate the potential use of TPO in a variety of contexts , but it is too early to evaluate its benefit in reducing platelet transfusion .

Preclinical and clinical studies demonstrate the potential use of <protein>TPO</protein> in a variety of contexts , but it is too early to evaluate its benefit in reducing platelet transfusion .


TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3 .

<protein>TAL1</protein> and <protein>LIM-only proteins</protein> synergistically induce <protein>retinaldehyde dehydrogenase 2</protein> expression in T-cell acute lymphoblastic leukemia by acting as cofactors for <protein>GATA3</protein> .


Previously , we have shown that TAL1 and the LIM-only protein gene ( LMO ) are regularly coactivated in T-cell acute lymphoblastic leukemia ( T-ALL ) .

Previously , we have shown that <protein>TAL1</protein> and the <dna>LIM-only protein gene</dna> ( <dna>LMO</dna> ) are regularly coactivated in T-cell acute lymphoblastic leukemia ( T-ALL ) .


This observation is likely to relate to the findings that TAL1 and LMO are highly synergistic in T-cell tumorigenesis in double-transgenic mice .

This observation is likely to relate to the findings that <protein>TAL1</protein> and <protein>LMO</protein> are highly synergistic in T-cell tumorigenesis in double-transgenic mice .


To understand the molecular mechanisms of functional synergy between TAL1 and LMO in tumorigenesis and transcriptional regulation , we tried to identify downstream target genes regulated by TAL1 and LMO by a subtractive PCR method .

To understand the molecular mechanisms of functional synergy between <protein>TAL1</protein> and <protein>LMO</protein> in tumorigenesis and transcriptional regulation , we tried to identify <dna>downstream target genes</dna> regulated by <protein>TAL1</protein> and <protein>LMO</protein> by a subtractive PCR method .


One of the isolated genes , that for retinaldehyde dehydrogenase 2 ( RALDH2 ) , was regularly expressed in most of the T-ALL cell lines that coexpressed TAL1 and LMO .

One of the isolated genes , that for <protein>retinaldehyde dehydrogenase 2</protein> ( <protein>RALDH2</protein> ) , was regularly expressed in most of the <cell_line>T-ALL cell lines</cell_line> that coexpressed <protein>TAL1</protein> and <protein>LMO</protein> .


Exogenously transfected TAL1 and LMO , but not either alone , induced RALDH2 expression in a T-ALL cell line , HPB-ALL , not expressing endogeneous TAL1 or LMO .

Exogenously transfected <protein>TAL1</protein> and <protein>LMO</protein> , but not either alone , induced <protein>RALDH2</protein> expression in a <cell_line>T-ALL cell line</cell_line> , <cell_line>HPB-ALL</cell_line> , not expressing endogeneous <protein>TAL1</protein> or <protein>LMO</protein> .


The RALDH2 transcripts in T-ALL were , however , mostly initiated within the second intron .

The <rna>RALDH2 transcripts</rna> in T-ALL were , however , mostly initiated within the <rna>second intron</rna> .