Compared with the interaction of VDR with RXR or GRIP-1 , the differentiation dose-response most closely correlated to the ligand-dependent recruitment of the DRIP coactivator complex to VDR and to the ability of the receptor to activate transcription in a cell-free system .

Compared with the interaction of <protein>VDR</protein> with <protein>RXR</protein> or <protein>GRIP-1</protein> , the differentiation dose-response most closely correlated to the ligand-dependent recruitment of the <protein>DRIP coactivator complex</protein> to <protein>VDR</protein> and to the ability of the receptor to activate transcription in a cell-free system .


These results provide compelling links between the efficiency of the 20-epi analogue in inducing VDR /DRIP interactions , transactivation in vitro , and its enhanced ability to induce cellular differentiation .

These results provide compelling links between the efficiency of the 20-epi analogue in inducing <protein>VDR</protein> /DRIP interactions , transactivation in vitro , and its enhanced ability to induce cellular differentiation .


SLP-76 and Vav function in separate , but overlapping pathways to augment interleukin-2 promoter activity .

<protein>SLP-76</protein> and <protein>Vav</protein> function in separate , but overlapping pathways to augment <dna>interleukin-2 promoter</dna> activity .


SLP-76 and Vav , two hematopoietic cell specific molecules , are critical for T cell development and activation .

<protein>SLP-76</protein> and <protein>Vav</protein> , two <protein>hematopoietic cell specific molecules</protein> , are critical for T cell development and activation .


Following T cell antigen receptor stimulation , SLP-76 and Vav both undergo tyrosine phosphorylation and associate with each other via the SH2 domain of Vav and phosphorylated tyrosines of SLP-76 .

Following <protein>T cell antigen receptor</protein> stimulation , <protein>SLP-76</protein> and <protein>Vav</protein> both undergo tyrosine phosphorylation and associate with each other via the SH2 domain of <protein>Vav</protein> and phosphorylated tyrosines of <protein>SLP-76</protein> .


Furthermore , SLP-76 and Vav have a synergistic effect on interleukin ( IL ) -2 promoter activity in T cells .

Furthermore , <protein>SLP-76</protein> and <protein>Vav</protein> have a synergistic effect on <dna>interleukin ( IL ) -2 promoter</dna> activity in <cell_line>T cells</cell_line> .


In this report , we show that two tyrosines , Tyr-113 and Tyr-128 , of SLP-76 are required for its binding to Vav , both in vitro and in intact cells .

In this report , we show that two tyrosines , Tyr-113 and Tyr-128 , of <protein>SLP-76</protein> are required for its binding to <protein>Vav</protein> , both in vitro and in <cell_type>intact cells</cell_type> .


Surprisingly , we find also that the interaction between SLP-76 and Vav is not required for their cooperation in augmenting IL-2 promoter activity , as the two molecules appear to function in different signaling pathways upstream of IL-2 gene expression .

Surprisingly , we find also that the interaction between <protein>SLP-76</protein> and <protein>Vav</protein> is not required for their cooperation in augmenting <dna>IL-2 promoter</dna> activity , as the two molecules appear to function in different signaling pathways upstream of <dna>IL-2 gene</dna> expression .


Overexpression of SLP-76 in the Jurkat T cell line potentiates the activities of both nuclear factor of activated T cells and AP-1 transcription factors .

Overexpression of <protein>SLP-76</protein> in the <cell_line>Jurkat T cell line</cell_line> potentiates the activities of both <protein>nuclear factor of activated T cells</protein> and <protein>AP-1 transcription factors</protein> .


In contrast , overexpression of Vav leads to enhanced nuclear factor of activated T cells activity without affecting AP-1 .

In contrast , overexpression of <protein>Vav</protein> leads to enhanced <protein>nuclear factor of activated T cells</protein> activity without affecting <protein>AP-1</protein> .


Additionally , overexpression of Vav , but not SLP-76 , augments CD28-induced IL-2 promoter activity .

Additionally , overexpression of <protein>Vav</protein> , but not <protein>SLP-76</protein> , augments CD28-induced <dna>IL-2 promoter</dna> activity .


These findings suggest that the synergy between SLP-76 and Vav in regulating IL-2 gene expression reflects the cooperation between different signaling pathways .

These findings suggest that the synergy between <protein>SLP-76</protein> and <protein>Vav</protein> in regulating <dna>IL-2 gene</dna> expression reflects the cooperation between different signaling pathways .


Rel/NF-kappaB can trigger the Notch signaling pathway by inducing the expression of Jagged1 , a ligand for Notch receptors .

<protein>Rel/NF-kappaB</protein> can trigger the Notch signaling pathway by inducing the expression of <protein>Jagged1</protein> , a ligand for <protein>Notch receptors</protein> .


Jagged1 belongs to the DSL family of ligands for Notch receptors that control the proliferation and differentiation of various cell lineages .

<protein>Jagged1</protein> belongs to the <protein>DSL family of ligands</protein> for <protein>Notch receptors</protein> that control the proliferation and differentiation of various <cell_type>cell lineages</cell_type> .


However , little is known about the transcription factors that regulate its expression .

However , little is known about the <protein>transcription factors</protein> that regulate its expression .


Here , we show that Jagged1 is a Rel/NF-kappaB-responsive gene .

Here , we show that <protein>Jagged1</protein> is a <dna>Rel/NF-kappaB-responsive gene</dna> .


Both c-Rel and RelA induced jagged1 gene expression , whereas a mutant defective for transactivation did not .

Both <protein>c-Rel</protein> and <protein>RelA</protein> induced jagged1 gene expression , whereas a mutant defective for transactivation did not .


Importantly , jagged1 transcripts were also upregulated by endogenous NF-kappaB activation and this effect was inhibited by a dominant mutant of IkappaBalpha , a physiological inhibitor of NF-kappaB .

Importantly , <protein>jagged1 transcripts</protein> were also upregulated by endogenous <protein>NF-kappaB</protein> activation and this effect was inhibited by a dominant mutant of <protein>IkappaBalpha</protein> , a physiological inhibitor of <protein>NF-kappaB</protein> .


Cell surface expression of Jagged1 in c-Rel-expressing cell monolayers led to a functional interaction with lymphocytes expressing the Notch1/TAN-1 receptor .

Cell surface expression of <protein>Jagged1</protein> in <cell_line>c-Rel-expressing cell monolayers</cell_line> led to a functional interaction with <cell_type>lymphocytes</cell_type> expressing the <protein>Notch1/TAN-1 receptor</protein> .


This correlated with the initiation of signaling downstream of Notch , as evidenced by increased levels of HES-1 transcripts in co-cultivated T cells and of CD23 transcripts in co-cultivated B cells .

This correlated with the initiation of signaling downstream of Notch , as evidenced by increased levels of <rna>HES-1 transcripts</rna> in <cell_line>co-cultivated T cells</cell_line> and of <rna>CD23 transcripts</rna> in co-cultivated <cell_type>B cells</cell_type> .


Consistent with its Rel/NF-kappaB -dependent induction , Jagged1 was found to be highly expressed in splenic B cells where c-Rel is expressed constitutively .

Consistent with its <protein>Rel/NF-kappaB</protein> -dependent induction , <protein>Jagged1</protein> was found to be highly expressed in <cell_type>splenic B cells</cell_type> where <protein>c-Rel</protein> is expressed constitutively .


These results demonstrate that c-Rel can trigger the Notch signaling pathway in neighboring cells by inducing jagged1 gene expression , and suggest a role for Jagged1 in B-cell activation , differentiation or function .

These results demonstrate that <protein>c-Rel</protein> can trigger the Notch signaling pathway in neighboring cells by inducing jagged1 gene expression , and suggest a role for <protein>Jagged1</protein> in B-cell activation , differentiation or function .


These findings also highlight the potential for an interplay between the Notch and NF-kappaB signaling pathways in the immune system .


Bacterial peptidoglycan induces CD14 -dependent activation of transcription factors CREB/ATF and AP-1 .

Bacterial peptidoglycan induces <protein>CD14</protein> -dependent activation of <protein>transcription factors</protein> <protein>CREB/ATF</protein> and <protein>AP-1</protein> .


Peptidoglycan ( PGN ) , the major cell wall component of Gram-positive bacteria , induces secretion of cytokines in macrophages through CD14 , the pattern recognition receptor that binds lipopolysaccharide and other microbial products .

Peptidoglycan ( PGN ) , the major cell wall component of Gram-positive bacteria , induces secretion of <protein>cytokines</protein> in <cell_type>macrophages</cell_type> through <protein>CD14</protein> , the pattern recognition receptor that binds lipopolysaccharide and other microbial products .


To begin to elucidate the mechanisms that regulate the transcription of cytokine genes , we wanted to determine which transcription factors are activated by PGN in mouse RAW264.7 and human THP-1 macrophage cells .

To begin to elucidate the mechanisms that regulate the transcription of <dna>cytokine genes</dna> , we wanted to determine which <protein>transcription factors</protein> are activated by PGN in <cell_line>mouse RAW264.7</cell_line> and <cell_line>human THP-1 macrophage cells</cell_line> .


Our results demonstrated that : ( i ) PGN induced phosphorylation of the transcription factors ATF-1 and CREB ; ( ii ) ATF-1 and CREB bound DNA as a dimer and induced transcriptional activation of a CRE reporter plasmid , which was inhibited by dominant negative CREB and ATF-1 ; ( iii ) PGN induced phosphorylation of c-Jun , protein synthesis of JunB and c-Fos , and transcriptional activation of the AP-1 reporter plasmid , which was inhibited by dominant negative c-Fos ; and ( iv ) PGN-induced activation of CREB/ATF and AP-1 was mediated through CD14 .

Our results demonstrated that : ( i ) PGN induced phosphorylation of the <protein>transcription factors</protein> <protein>ATF-1</protein> and <protein>CREB</protein> ; ( ii ) <protein>ATF-1</protein> and <protein>CREB</protein> bound DNA as a dimer and induced transcriptional activation of a <dna>CRE reporter plasmid</dna> , which was inhibited by dominant negative <protein>CREB</protein> and <protein>ATF-1</protein> ; ( iii ) PGN induced phosphorylation of <protein>c-Jun</protein> , protein synthesis of <protein>JunB</protein> and <protein>c-Fos</protein> , and transcriptional activation of the <dna>AP-1 reporter plasmid</dna> , which was inhibited by dominant negative <protein>c-Fos</protein> ; and ( iv ) PGN-induced activation of <protein>CREB/ATF</protein> and <protein>AP-1</protein> was mediated through <protein>CD14</protein> .


This is the first study to demonstrate activation of CREB/ATF and AP-1 transcription factors by PGN or by any other component of Gram-positive bacteria .

This is the first study to demonstrate activation of <protein>CREB/ATF</protein> and <protein>AP-1 transcription factors</protein> by PGN or by any other component of Gram-positive bacteria .


Glucocorticoid receptors are down-regulated in inflamed colonic mucosa but not in peripheral blood mononuclear cells from patients with inflammatory bowel disease [ see comments ]

<protein>Glucocorticoid receptors</protein> are down-regulated in inflamed colonic mucosa but not in <cell_type>peripheral blood mononuclear cells</cell_type> from patients with inflammatory bowel disease [ see comments ]


BACKGROUND : Growing evidence indicates that the immune system and the hypothalamic-pituitary-adrenal system are linked by several mechanisms , for example intracellular glucocorticoid receptors ( hGR ) .

BACKGROUND : Growing evidence indicates that the immune system and the hypothalamic-pituitary-adrenal system are linked by several mechanisms , for example intracellular <protein>glucocorticoid receptors</protein> ( <protein>hGR</protein> ) .


Glucocorticoids are the standard treatment of acute attacks of inflammatory bowel disease ( IBD ) .


Binding of glucocorticoids to hGR down-regulates the transcription of inflammatory genes that can propagate IBD .

Binding of glucocorticoids to <protein>hGR</protein> down-regulates the transcription of <dna>inflammatory genes</dna> that can propagate IBD .


PATIENTS AND METHODS : IBD patients were either treated with 5-60 mg of prednisolone for more than 1 week or were without glucocorticoid treatment for more than 4 weeks .


hGR levels were determined from isolated cytosol of peripheral blood mononuclear cells ( PBMCs ) or mucosal biopsies using a radioassay with [ 3H ] -dexamethasone .

<protein>hGR</protein> levels were determined from isolated cytosol of <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) or mucosal biopsies using a radioassay with [ 3H ] -dexamethasone .


Interleukin ( IL ) 6 levels were determined by enzyme-linked immunosorbent assay ( ELISA ) .


RESULTS : The systemic ( PBMC ) hGR levels of corticosteroid-treated IBD patients were significantly lower than those of control subjects ( 59.6 +/- 57.1 dpm mg-1 cytosol protein vs .

RESULTS : The systemic ( PBMC ) <protein>hGR</protein> levels of corticosteroid-treated IBD patients were significantly lower than those of control subjects ( 59.6 +/- 57.1 dpm mg-1 <protein>cytosol protein</protein> vs .


227.0 +/- 90.8 dpm mg-1 cytosol protein , P = 0.007 ) and IBD patients not receiving glucocorticoid treatment ( 179.7 +/- 171.3 dpm mg-1 cytosol protein , P = 0.002 ) .

227.0 +/- 90.8 dpm mg-1 <protein>cytosol protein</protein> , P = 0.007 ) and IBD patients not receiving glucocorticoid treatment ( 179.7 +/- 171.3 dpm mg-1 <protein>cytosol protein</protein> , P = 0.002 ) .


Systemic hGR levels in untreated IBD patients did not differ significantly from those in control subjects .

Systemic <protein>hGR</protein> levels in untreated IBD patients did not differ significantly from those in control subjects .


In patients with connective tissue diseases , systemic hGR levels were also found to be decreased in the absence of glucocorticoid treatment .

In patients with connective tissue diseases , systemic <protein>hGR</protein> levels were also found to be decreased in the absence of glucocorticoid treatment .


Systemic hGR levels in patients with Crohn 's disease ( CD ) treated with steroids ( 66.6 +/- 61.0 dpm mg-1 cytosol protein ) were not different from those in patients with ulcerative colitis ( UC ) ( 56.1 +/- 51.6 dpm mg-1 cytosol protein ) .

Systemic <protein>hGR</protein> levels in patients with Crohn 's disease ( CD ) treated with steroids ( 66.6 +/- 61.0 dpm mg-1 <protein>cytosol protein</protein> ) were not different from those in patients with ulcerative colitis ( UC ) ( 56.1 +/- 51.6 dpm mg-1 <protein>cytosol protein</protein> ) .


In contrast to these findings , mucosal hGR levels were significantly decreased in both steroid-treated ( 18.0 +/- 15.5 ) and not steroid-treated ( 37.8 +/- 30.5 ) patients compared with control subjects ( 125.6 +/- 97.1 ; P = 0.00009 and P = 0.0008 respectively ) .

In contrast to these findings , mucosal <protein>hGR</protein> levels were significantly decreased in both steroid-treated ( 18.0 +/- 15.5 ) and not steroid-treated ( 37.8 +/- 30.5 ) patients compared with control subjects ( 125.6 +/- 97.1 ; P = 0.00009 and P = 0.0008 respectively ) .


IL-6 levels in all IBD groups with and without steroids were significantly different from those in control subjects .


CONCLUSION : In IBD there is no difference in systemic hGR levels between not steroid-treated patients and control subjects , in spite of inflammatory activity ( IL-6 ) .

CONCLUSION : In IBD there is no difference in systemic <protein>hGR</protein> levels between not steroid-treated patients and control subjects , in spite of inflammatory activity ( <protein>IL-6</protein> ) .


Mucosal hGR levels were decreased independently of treatment , probably leading to a decreased protection against NF-kappaB action in the intestinal mucosa .

Mucosal <protein>hGR</protein> levels were decreased independently of treatment , probably leading to a decreased protection against <protein>NF-kappaB</protein> action in the intestinal mucosa .


ICSAT overexpression is not sufficient to cause adult T-cell leukemia or multiple myeloma .

<protein>ICSAT</protein> overexpression is not sufficient to cause adult T-cell leukemia or multiple myeloma .


ICSAT ( Interferon Consensus Sequence binding protein for Activated T cells ) is a lymphocyte-specific member of the interferon regulatory factor ( IRF ) family of transcription factors , originally identified through Southwestern screening of the ATL ( Adult T-cell leukemia ) -16T expression library .

<protein>ICSAT</protein> ( <protein>Interferon Consensus Sequence binding protein for Activated T cells</protein> ) is a lymphocyte-specific member of the <protein>interferon regulatory factor ( IRF ) family</protein> of transcription factors , originally identified through Southwestern screening of the <dna>ATL ( Adult T-cell leukemia ) -16T expression library</dna> .


In this study , we created transgenic mice overexpressing ICSAT in lymphocytes .

In this study , we created transgenic mice overexpressing <protein>ICSAT</protein> in <cell_type>lymphocytes</cell_type> .


Although spontaneous tumorigenesis was not observed , IL-2 production with Concanavalin A stimulation was significantly increased in transgenic mice overexpressing ICSAT .

Although spontaneous tumorigenesis was not observed , <protein>IL-2</protein> production with Concanavalin A stimulation was significantly increased in transgenic mice overexpressing <protein>ICSAT</protein> .


ICSAT overexpression in lymphocytes seems insufficient for the leukemogenesis of ATL or multiple myeloma ( MM ) , however , it may regulate T cell activation and its overexpression may lead to leukemogenesis via controlling IL-2 production .

<protein>ICSAT</protein> overexpression in <cell_type>lymphocytes</cell_type> seems insufficient for the leukemogenesis of ATL or multiple myeloma ( MM ) , however , it may regulate T cell activation and its overexpression may lead to leukemogenesis via controlling <protein>IL-2</protein> production .


Copyright 1999 Academic Press .


Altered memory T cell differentiation in patients with early rheumatoid arthritis .

Altered <cell_type>memory T cell</cell_type> differentiation in patients with early rheumatoid arthritis .


The chronic immune response in rheumatoid arthritis ( RA ) might be driven by activated Th1 cells without sufficient Th2 cell differentiation to down-modulate inflammation .


To test whether disordered memory T cell differentiation contributes to the typical Th1-dominated chronic inflammation in RA we investigated differentiation of resting CD4+ memory T cells in patients with early ( 6 wk to 12 mo ) untreated RA and in age- and sex-matched healthy controls in vitro .

To test whether disordered <cell_type>memory T cell</cell_type> differentiation contributes to the typical Th1-dominated chronic inflammation in RA we investigated differentiation of <cell_type>resting CD4+ memory T cells</cell_type> in patients with early ( 6 wk to 12 mo ) untreated RA and in age- and sex-matched healthy controls in vitro .


No difference in cytokine secretion profiles of freshly isolated memory T cells was detected between patients and controls .

No difference in <protein>cytokine</protein> secretion profiles of <cell_type>freshly isolated memory T cells</cell_type> was detected between patients and controls .


A cell culture system was then employed that permitted the differentiation of Th effectors from resting memory T cells by short term priming .

A <cell_line>cell culture system</cell_line> was then employed that permitted the differentiation of <protein>Th effectors</protein> from <cell_type>resting memory T cells</cell_type> by short term priming .


Marked differences were found in response to priming .


Th2 cells could be induced in all healthy controls by priming with anti-CD28 in the absence of TCR ligation .

<cell_line>Th2 cells</cell_line> could be induced in all healthy controls by priming with <protein>anti-CD28</protein> in the absence of <protein>TCR</protein> ligation .


By contrast , priming under those conditions resulted in Th2 differentiation in only 9 of 24 RA patients .


Exogenous IL-4 could overcome the apparent Th2 differentiation defect in seven patients but was without effect in the remaining eight patients .

Exogenous <protein>IL-4</protein> could overcome the apparent Th2 differentiation defect in seven patients but was without effect in the remaining eight patients .


In all patients a marked decrease in IL-2-producing cells and a significant increase in well-differentiated Th1 cells that produced IFN-gamma but not IL-2 were evident after priming with anti-CD3 and anti-CD28 .

In all patients a marked decrease in <cell_type>IL-2-producing cells</cell_type> and a significant increase in well-differentiated <cell_type>Th1 cells</cell_type> that produced <protein>IFN-gamma</protein> but not <protein>IL-2</protein> were evident after priming with <protein>anti-CD3</protein> and <protein>anti-CD28</protein> .


The data suggest that CD4+ memory T cells from patients with early untreated RA manifest an intrinsic abnormality in their ability to differentiate into specific cytokine-producing effector cells that might contribute to the characteristic Th1-dominated chronic ( auto ) immune inflammation in RA .

The data suggest that <cell_type>CD4+ memory T cells</cell_type> from patients with early untreated RA manifest an intrinsic abnormality in their ability to differentiate into specific <cell_type>cytokine-producing effector cells</cell_type> that might contribute to the characteristic Th1-dominated chronic ( auto ) immune inflammation in RA .


The intracellular parasite Theileria parva protects infected T cells from apoptosis .

The intracellular parasite Theileria parva protects <cell_type>infected T cells</cell_type> from apoptosis .


Parasites have evolved a plethora of strategies to ensure their survival .


The intracellular parasite Theileria parva secures its propagation and spreads through the infected animal by infecting and transforming T cells , inducing their continuous proliferation and rendering them metastatic .

The intracellular parasite Theileria parva secures its propagation and spreads through the infected animal by infecting and transforming <cell_type>T cells</cell_type> , inducing their continuous proliferation and rendering them metastatic .


In previous work , we have shown that the parasite induces constitutive activation of the transcription factor NF-kappaB , by inducing the constitutive degradation of its cytoplasmic inhibitors .

In previous work , we have shown that the parasite induces constitutive activation of the <protein>transcription factor</protein> <protein>NF-kappaB</protein> , by inducing the constitutive degradation of its <protein>cytoplasmic inhibitors</protein> .


The biological significance of NF-kappaB activation in T. parva-infected cells , however , has not yet been defined .

The biological significance of <protein>NF-kappaB</protein> activation in <cell_type>T. parva-infected cells</cell_type> , however , has not yet been defined .


Cells that have been transformed by viruses or oncogenes can persist only if they manage to avoid destruction by the apoptotic mechanisms that are activated on transformation and that contribute to maintain cellular homeostasis .

Cells that have been transformed by viruses or <dna>oncogenes</dna> can persist only if they manage to avoid destruction by the apoptotic mechanisms that are activated on transformation and that contribute to maintain cellular homeostasis .


We now demonstrate that parasite-induced NF-kappaB activation plays a crucial role in the survival of T. parva-transformed T cells by conveying protection against an apoptotic signal that accompanies parasite-mediated transformation .

We now demonstrate that parasite-induced <protein>NF-kappaB</protein> activation plays a crucial role in the survival of <cell_type>T. parva-transformed T cells</cell_type> by conveying protection against an apoptotic signal that accompanies parasite-mediated transformation .


Consequently , inhibition of NF-kappaB nuclear translocation and the expression of dominant negative mutant forms of components of the NF-kappaB activation pathway , such as IkappaBalpha or p65 , prompt rapid apoptosis of T. parva-transformed T cells .

Consequently , inhibition of <protein>NF-kappaB</protein> nuclear translocation and the expression of <protein>dominant negative mutant</protein> forms of components of the <protein>NF-kappaB</protein> activation pathway , such as <protein>IkappaBalpha</protein> or <protein>p65</protein> , prompt rapid apoptosis of <cell_type>T. parva-transformed T cells</cell_type> .


Our findings offer important insights into parasite survival strategies and demonstrate that parasite-induced constitutive NF-kappaB activation is an essential step in maintaining the transformed phenotype of the infected cells .

Our findings offer important insights into parasite survival strategies and demonstrate that parasite-induced constitutive <protein>NF-kappaB</protein> activation is an essential step in maintaining the transformed phenotype of the <cell_type>infected cells</cell_type> .


A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria [ see comments ]

A polymorphism that affects <protein>OCT-1</protein> binding to the <dna>TNF promoter region</dna> is associated with severe malaria [ see comments ]


Genetic variation in cytokine promoter regions is postulated to influence susceptibility to infection , but the molecular mechanisms by which such polymorphisms might affect gene regulation are unknown .

Genetic variation in <dna>cytokine promoter regions</dna> is postulated to influence susceptibility to infection , but the molecular mechanisms by which such polymorphisms might affect gene regulation are unknown .


Through systematic DNA footprinting of the TNF ( encoding tumour necrosis factor , TNF ) promoter region , we have identified a single nucleotide polymorphism ( SNP ) that causes the helix-turn-helix transcription factor OCT-1 to bind to a novel region of complex protein-DNA interactions and alters gene expression in human monocytes .

Through systematic DNA footprinting of the TNF ( encoding tumour necrosis factor , TNF ) promoter region , we have identified a single nucleotide polymorphism ( SNP ) that causes the helix-turn-helix <protein>transcription factor</protein> OCT-1 to bind to a novel region of complex protein-DNA interactions and alters gene expression in <cell_type>human monocytes</cell_type> .


The OCT-1-binding genotype , found in approximately 5 % of Africans , is associated with fourfold increased susceptibility to cerebral malaria in large case-control studies of West African and East African populations , after correction for other known TNF polymorphisms and linked HLA alleles .

The OCT-1-binding genotype , found in approximately 5 % of Africans , is associated with fourfold increased susceptibility to cerebral malaria in large case-control studies of West African and East African populations , after correction for other known TNF polymorphisms and linked <dna>HLA alleles</dna> .


UV-induced CYP1A1 gene expression in human cells is mediated by tryptophan .

UV-induced <protein>CYP1A1</protein> gene expression in human cells is mediated by tryptophan .


Induction of cytochrome P-4501A1 ( CYP1A1 ) activity by UV has been observed earlier in animal studies via a mechanism that has not yet been resolved .

Induction of <protein>cytochrome P-4501A1</protein> ( <protein>CYP1A1</protein> ) activity by UV has been observed earlier in animal studies via a mechanism that has not yet been resolved .


Our previous data have indicated that formylated indolocarbazoles which are formed by UV irradiation of tryptophan solutions are very potent Ah-receptor agonists .


To evaluate the effect of UV light on cytochrome P4501A1 gene expression , we studied the induction of CYP1A1 mRNA by UV irradiation of cultured human keratinocytes ( HaCaT cell line ) , primary human blood lymphocytes and mouse Hepa-1 cells .

To evaluate the effect of UV light on <protein>cytochrome P4501A1</protein> gene expression , we studied the induction of <rna>CYP1A1 mRNA</rna> by UV irradiation of <cell_line>cultured human keratinocytes</cell_line> ( <cell_line>HaCaT cell line</cell_line> ) , <cell_type>primary human blood lymphocytes</cell_type> and <cell_line>mouse Hepa-1 cells</cell_line> .


The cells were exposed to UV light delivered by a bank of 6 Philips TL20/12RS sun lamps emitting primarily in the UVB range in the absence and presence of tryptophan .


A semiquantitative reverse transcriptase -linked polymerase chain reaction ( RT-PCR ) was used for analysis of gene expression in the treated cells .

A semiquantitative <protein>reverse transcriptase</protein> -linked polymerase chain reaction ( RT-PCR ) was used for analysis of gene expression in the <cell_type>treated cells</cell_type> .


The results show that the CYP1A1 mRNA level induced by UV in the presence of tryptophan was higher than that induced by UV alone in both HaCaT cells and lymphocytes after 3 h of incubation post-UV irradiation .

The results show that the <rna>CYP1A1 mRNA</rna> level induced by UV in the presence of tryptophan was higher than that induced by UV alone in both <cell_line>HaCaT cells</cell_line> and <cell_type>lymphocytes</cell_type> after 3 h of incubation post-UV irradiation .


To find out if the induction by UV light is caused by the formation of an Ah receptor ligand , Hepa-1 wild-type and Ah receptor deficient c12 cell lines were applied .

To find out if the induction by UV light is caused by the formation of an Ah receptor ligand , <cell_line>Hepa-1 wild-type and Ah receptor deficient c12 cell lines</cell_line> were applied .


Wild-type ( wt ) cells were inducible either by the tryptophan photoproduct 6-formylindolo [ 3 , 2-b ] carbazole ( FICZ ) or by UV-irradiation but very low or undetectable levels were observed in the c12 cells .

<cell_line>Wild-type ( wt ) cells</cell_line> were inducible either by the tryptophan photoproduct 6-formylindolo [ 3 , 2-b ] carbazole ( FICZ ) or by UV-irradiation but very low or undetectable levels were observed in the <cell_type>c12 cells</cell_type> .


This shows that the induction of gene expression by FICZ and UV is Ah receptor dependent .

This shows that the induction of gene expression by FICZ and UV is <protein>Ah receptor</protein> dependent .


Together , these results indicate that UV-induced CYP1A1 gene expression in mammalian cells is mediated by an Ah receptor ligand formed from tryptophan .

Together , these results indicate that UV-induced <protein>CYP1A1</protein> gene expression in <cell_type>mammalian cells</cell_type> is mediated by an <protein>Ah receptor</protein> ligand formed from tryptophan .


Thus , the photoproducts of tryptophan are suggested to be mediators of light via binding to the Ah receptor and as such also could have a role in light-regulated biological rhythms .

Thus , the photoproducts of tryptophan are suggested to be mediators of light via binding to the <protein>Ah receptor</protein> and as such also could have a role in light-regulated biological rhythms .


Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes .

Repression by <protein>Ikaros</protein> and <protein>Aiolos</protein> is mediated through <protein>histone deacetylase complexes</protein> .


Here we show that the lymphoid lineage-determining factors Ikaros and Aiolos can function as strong transcriptional repressors .

Here we show that the <protein>lymphoid lineage-determining factors</protein> <protein>Ikaros</protein> and <protein>Aiolos</protein> can function as <protein>strong transcriptional repressors</protein> .


This function is mediated through two repression domains and is dependent upon the promoter context and cell type .

This function is mediated through two <protein>repression domains</protein> and is dependent upon the promoter context and cell type .


Repression by Ikaros proteins correlates with hypo-acetylation of core histones at promoter sites and is relieved by histone deacetylase inhibitors .

Repression by <protein>Ikaros proteins</protein> correlates with hypo-acetylation of <protein>core histones</protein> at <dna>promoter sites</dna> and is relieved by <protein>histone deacetylase</protein> inhibitors .


Consistent with these findings , Ikaros and its repression domains can interact in vivo and in vitro with the mSin3 family of co-repressors which bind to histone deacetylases .

Consistent with these findings , <protein>Ikaros</protein> and its <protein>repression domains</protein> can interact in vivo and in vitro with the <protein>mSin3 family</protein> of co-repressors which bind to <protein>histone deacetylases</protein> .


Based on these and our recent findings of associations between Ikaros and Mi-2-HDAC , we propose that Ikaros family members modulate gene expression during lymphocyte development by recruiting distinct histone deacetylase complexes to specific promoters .

Based on these and our recent findings of associations between <protein>Ikaros</protein> and <protein>Mi-2-HDAC</protein> , we propose that <protein>Ikaros family members</protein> modulate gene expression during lymphocyte development by recruiting distinct <protein>histone deacetylase complexes</protein> to <dna>specific promoters</dna> .


Protein kinase B ( c-Akt ) , phosphatidylinositol 3-kinase , and STAT5 are activated by erythropoietin ( EPO ) in HCD57 erythroid cells but are constitutively active in an EPO-independent , apoptosis-resistant subclone ( HCD57-SREI cells ) .

<protein>Protein kinase B</protein> ( <protein>c-Akt</protein> ) , <protein>phosphatidylinositol 3-kinase</protein> , and <protein>STAT5</protein> are activated by <protein>erythropoietin</protein> ( <protein>EPO</protein> ) in <cell_line>HCD57 erythroid cells</cell_line> but are constitutively active in an <cell_line>EPO-independent , apoptosis-resistant subclone</cell_line> ( <cell_line>HCD57-SREI cells</cell_line> ) .


We found that erythropoietin ( EPO ) and stem cell factor ( SCF ) activated protein kinase B ( PKB/Akt ) in EPO-dependent HCD57 erythroid cells .

We found that <protein>erythropoietin</protein> ( <protein>EPO</protein> ) and <protein>stem cell factor</protein> ( <protein>SCF</protein> ) <protein>activated protein kinase B</protein> ( <protein>PKB/Akt</protein> ) in <cell_line>EPO-dependent HCD57 erythroid cells</cell_line> .


To better understand signals controlling proliferation and viability , erythroid cells that resist apoptosis in the absence of EPO were subcloned and characterized ( HCD57-SREI cells ) .

To better understand signals controlling proliferation and viability , erythroid cells that resist apoptosis in the absence of <protein>EPO</protein> were subcloned and characterized ( <cell_line>HCD57-SREI cells</cell_line> ) .


Constitutive activations of PKB/Akt , STAT5a , and STAT5b were noted in these EPO-independent cells .

Constitutive activations of <protein>PKB/Akt</protein> , <protein>STAT5a</protein> , and <protein>STAT5b</protein> were noted in these <cell_line>EPO-independent cells</cell_line> .


PI3-kinase activity was an upstream activator of PKB/Akt because the PI3-kinase inhibitor LY294002 blocked both constitutive PKB/Akt and factor-dependent PKB/Akt activity .

<protein>PI3-kinase</protein> activity was an upstream activator of <protein>PKB/Akt</protein> because the <protein>PI3-kinase</protein> inhibitor LY294002 blocked both constitutive <protein>PKB/Akt</protein> and factor-dependent <protein>PKB/Akt</protein> activity .


The LY294002 study showed that proliferation and viability of both HCD57-SREI and HCD57 cells correlated with the activity of PKB/Akt ; however , PKB/Akt activity alone did not protect these cells from apoptosis .

The LY294002 study showed that proliferation and viability of both <cell_line>HCD57-SREI</cell_line> and <cell_line>HCD57 cells</cell_line> correlated with the activity of <protein>PKB/Akt</protein> ; however , <protein>PKB/Akt</protein> activity alone did not protect these cells from apoptosis .


Treatment of HCD57 cells with SCF also activated PKB/Akt , but did not protect from apoptosis .

Treatment of <cell_line>HCD57 cells</cell_line> with <protein>SCF</protein> also activated <protein>PKB/Akt</protein> , but did not protect from apoptosis .


This result suggested that PKB/PI3-kinase activity is necessary but not sufficient to promote viability and/or proliferation .

This result suggested that <protein>PKB/PI3-kinase</protein> activity is necessary but not sufficient to promote viability and/or proliferation .


Constitutive STAT5 activity , activated through an unknown pathway not including JAK2 or EPOR , may act in concert with the constitutive PI3-kinase /PKB/Akt pathway to protect the EPO-independent HCD57-SREI cells from apoptosis and promote limited proliferation .

Constitutive <protein>STAT5</protein> activity , activated through an unknown pathway not including <protein>JAK2</protein> or <protein>EPOR</protein> , may act in concert with the constitutive <protein>PI3-kinase</protein> <protein>/PKB/Akt</protein> pathway to protect the <cell_line>EPO-independent HCD57-SREI cells</cell_line> from apoptosis and promote limited proliferation .


Disruption of alpha beta but not of gamma delta T cell development by overexpression of the helix-loop-helix protein Id3 in committed T cell progenitors .

Disruption of alpha beta but not of gamma delta T cell development by overexpression of the <protein>helix-loop-helix protein</protein> <protein>Id3</protein> in <cell_type>committed T cell progenitors</cell_type> .


Enforced expression of Id3 , which has the capacity to inhibit many basic helix-loop-helix ( bHLH ) transcription factors , in human CD34 ( + ) hematopoietic progenitor cells that have not undergone T cell receptor ( TCR ) gene rearrangements inhibits development of the transduced cells into TCRalpha beta and gamma delta cells in a fetal thymic organ culture ( FTOC ) .

Enforced expression of <protein>Id3</protein> , which has the capacity to inhibit many <protein>basic helix-loop-helix ( bHLH ) transcription factors</protein> , in <cell_type>human CD34 ( + ) hematopoietic progenitor cells</cell_type> that have not undergone <dna>T cell receptor ( TCR ) gene rearrangements</dna> inhibits development of the <cell_type>transduced cells</cell_type> into <cell_line>TCRalpha beta and gamma delta cells</cell_line> in a <cell_line>fetal thymic organ culture</cell_line> ( <cell_line>FTOC</cell_line> ) .


Here we document that overexpression of Id3 , in progenitors that have initiated TCR gene rearrangements ( pre-T cells ) , inhibits development into TCRalpha beta but not into TCRgamma delta T cells .

Here we document that overexpression of <protein>Id3</protein> , in <cell_type>progenitors</cell_type> that have initiated <dna>TCR gene rearrangements</dna> ( <cell_type>pre-T cells</cell_type> ) , inhibits development into <cell_line>TCRalpha beta</cell_line> but not into <cell_line>TCRgamma delta T cells</cell_line> .


Furthermore , Id3 impedes expression of recombination activating genes and downregulates pre-Talpha mRNA .

Furthermore , <protein>Id3</protein> impedes expression of recombination activating genes and downregulates <rna>pre-Talpha mRNA</rna> .


These observations suggest possible mechanisms by which Id3 overexpression can differentially affect development of pre-T cells into TCRalpha beta and gamma delta cells .

These observations suggest possible mechanisms by which <protein>Id3</protein> overexpression can differentially affect development of <cell_type>pre-T cells</cell_type> into <cell_line>TCRalpha beta and gamma delta cells</cell_line> .


We also observed that cell surface CD4 ( - ) CD8 ( - ) CD3 ( - ) cells with rearranged TCR genes developed from Id3-transduced but not from control-transduced pre-T cells in an FTOC .

We also observed that <cell_type>cell surface CD4 ( - ) CD8 ( - ) CD3 ( - ) cells</cell_type> with <dna>rearranged TCR genes</dna> developed from <cell_line>Id3-transduced</cell_line> but not from <cell_line>control-transduced pre-T cells</cell_line> in an <cell_line>FTOC</cell_line> .


These cells had properties of both natural killer ( NK ) and pre-T cells .

These cells had properties of both <cell_type>natural killer</cell_type> ( <cell_type>NK</cell_type> ) and <cell_type>pre-T cells</cell_type> .


These findings suggest that bHLH factors are required to control T cell development after the T/NK developmental checkpoint .

These findings suggest that <protein>bHLH factors</protein> are required to control T cell development after the T/NK developmental checkpoint .


HIV-1 reactivation in resting peripheral blood mononuclear cells of infected adults upon in vitro CD4 cross-linking by ligands of the CDR2-loop in extracellular domain 1 .

HIV-1 reactivation in <cell_type>resting peripheral blood mononuclear cells</cell_type> of infected adults upon in vitro <protein>CD4</protein> cross-linking by ligands of the <protein>CDR2-loop</protein> in <protein>extracellular domain 1</protein> .


HIV-1 infects resting peripheral blood mononuclear cells ( PBMCs ) but remains inactive state until subsequent cell activation .

HIV-1 infects <cell_type>resting peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) but remains inactive state until subsequent cell activation .


We have demonstrated that the cross-linking of cell surface CD4 by gp120-anti-gp120 immune complexes or heat-inactivated HIV-1 ( iHIV-1 ) is sufficient to trigger activation signals leading to virus reactivation ( 9 ) .

We have demonstrated that the cross-linking of <protein>cell surface CD4</protein> by <protein>gp120-anti-gp120 immune complexes</protein> or heat-inactivated HIV-1 ( iHIV-1 ) is sufficient to trigger activation signals leading to virus reactivation ( 9 ) .


In this study , we demonstrate that NF-kappaB nuclear translocation and stimulation of virus production by iHIV-1 were strictly linked to the concentrations of viral proteins used as exogenous stimuli .

In this study , we demonstrate that <protein>NF-kappaB</protein> nuclear translocation and stimulation of virus production by iHIV-1 were strictly linked to the concentrations of <protein>viral proteins</protein> used as exogenous stimuli .


Moreover , we further investigated the physiologic relevance of these observations .


When submitted to an in vitro CD4 cross-linking by iHIV-1 , PBMCs from HIV-1-infected patients were found to produce virus .

When submitted to an in vitro <protein>CD4</protein> cross-linking by iHIV-1 , <cell_type>PBMCs</cell_type> from HIV-1-infected patients were found to produce virus .


This viral reactivation was associated with increased NF-kappaB nuclear translocation in patients ' PBMCs .

This viral reactivation was associated with increased <protein>NF-kappaB</protein> nuclear translocation in patients ' <cell_type>PBMCs</cell_type> .


Additionally , virus reactivation in resting PBMCs infected in vitro with HIV-1 was found to be specifically induced by ligands of the CDR2-loop in domain 1 ( D1 ) of CD4 ( virus envelope and anti-CD4 monoclonal antibodies ) .

Additionally , virus reactivation in <cell_type>resting PBMCs</cell_type> infected in vitro with HIV-1 was found to be specifically induced by ligands of the <protein>CDR2-loop</protein> in <protein>domain 1</protein> ( <protein>D1</protein> ) of <protein>CD4</protein> ( <protein>virus envelope and anti-CD4 monoclonal antibodies</protein> ) .


In contrast , virus reactivation was not observed following CD4 oligomerization by antibodies that bind other epitopes in D1 , including the D1/CDR3-loop .

In contrast , virus reactivation was not observed following <protein>CD4</protein> oligomerization by <protein>antibodies</protein> that bind other epitopes in <protein>D1</protein> , including the <protein>D1/CDR3-loop</protein> .


Finally , soluble CD4 ( sCD4 ) prevented virus reactivation by D1/CDR2-loop ligands .

Finally , <protein>soluble CD4</protein> ( <protein>sCD4</protein> ) prevented virus reactivation by <protein>D1/CDR2-loop ligands</protein> .


Our results indicate that the signaling events initiated in PBMCs by oligomerization of CD4 at the D1/CDR2-loop can trigger HIV-1 upregulation in infected individuals .

Our results indicate that the signaling events initiated in <cell_type>PBMCs</cell_type> by oligomerization of <protein>CD4</protein> at the <protein>D1/CDR2-loop</protein> can trigger HIV-1 upregulation in infected individuals .


Signaling through the lymphotoxin-beta receptor stimulates HIV-1 replication alone and in cooperation with soluble or membrane-bound TNF-alpha .

Signaling through the <protein>lymphotoxin-beta receptor</protein> stimulates HIV-1 replication alone and in cooperation with soluble or <protein>membrane-bound TNF-alpha</protein> .


The level of ongoing HIV-1 replication within an individual is critical to HIV-1 pathogenesis .


Among host immune factors , the cytokine TNF-alpha has previously been shown to increase HIV-1 replication in various monocyte and T cell model systems .

Among host immune factors , the <protein>cytokine</protein> <protein>TNF-alpha</protein> has previously been shown to increase HIV-1 replication in various monocyte and T cell model systems .


Here , we demonstrate that signaling through the TNF receptor family member , the lymphotoxin-beta ( LT-beta ) receptor ( LT-betaR ) , also regulates HIV-1 replication .

Here , we demonstrate that signaling through the <protein>TNF</protein> receptor family member , the <protein>lymphotoxin-beta ( LT-beta ) receptor</protein> ( <protein>LT-betaR</protein> ) , also regulates HIV-1 replication .


Furthermore , HIV-1 replication is cooperatively stimulated when the distinct LT-betaR and TNF receptor systems are simultaneously engaged by their specific ligands .

Furthermore , HIV-1 replication is cooperatively stimulated when the distinct <protein>LT-betaR</protein> and <protein>TNF receptor systems</protein> are simultaneously engaged by their specific ligands .


Moreover , in a physiological coculture cellular assay system , we show that membrane-bound TNF-alpha and LT-alpha1beta2 act virtually identically to their soluble forms in the regulation of HIV-1 replication .

Moreover , in a physiological coculture cellular assay system , we show that <protein>membrane-bound TNF-alpha</protein> and <protein>LT-alpha1beta2</protein> act virtually identically to their soluble forms in the regulation of HIV-1 replication .


Thus , cosignaling via the LT-beta and TNF-alpha receptors is probably involved in the modulation of HIV-1 replication and the subsequent determination of HIV-1 viral burden in monocytes .

Thus , cosignaling via the <protein>LT-beta and TNF-alpha receptors</protein> is probably involved in the modulation of HIV-1 replication and the subsequent determination of HIV-1 viral burden in <cell_type>monocytes</cell_type> .


Intriguingly , surface expression of LT-alpha1beta2 is up-regulated on a T cell line acutely infected with HIV-1 , suggesting a positive feedback loop between HIV-1 infection , LT-alpha1beta2 expression , and HIV-1 replication .

Intriguingly , surface expression of <protein>LT-alpha1beta2</protein> is up-regulated on a <cell_line>T cell line</cell_line> acutely infected with HIV-1 , suggesting a positive feedback loop between HIV-1 infection , <protein>LT-alpha1beta2</protein> expression , and HIV-1 replication .


Given the critical role that LT-alpha1beta2 plays in lymphoid architecture , we speculate that LT-alpha1beta2 may be involved in HIV-associated abnormalities of the lymphoid organs .

Given the critical role that <protein>LT-alpha1beta2</protein> plays in lymphoid architecture , we speculate that <protein>LT-alpha1beta2</protein> may be involved in HIV-associated abnormalities of the lymphoid organs .


Monoclonal anti-endothelial cell antibodies from a patient with Takayasu arteritis activate endothelial cells from large vessels .

<protein>Monoclonal anti-endothelial cell antibodies</protein> from a patient with Takayasu arteritis activate endothelial cells from large vessels .


OBJECTIVE : To create monoclonal anti-endothelial cell antibodies ( mAECA ) from a patient with Takayasu arteritis to evaluate their ability to activate human umbilical vein endothelial cells ( HUVEC ) , and to characterize the mechanism of EC activation .

OBJECTIVE : To create <protein>monoclonal anti-endothelial cell antibodies</protein> ( <protein>mAECA</protein> ) from a patient with Takayasu arteritis to evaluate their ability to activate <cell_line>human umbilical vein endothelial cells</cell_line> ( <cell_line>HUVEC</cell_line> ) , and to characterize the mechanism of EC activation .


METHODS : A panel of mAECA was generated from peripheral blood lymphocytes of a patient with Takayasu arteritis , using Epstein-Barr virus transformation .

METHODS : A panel of <protein>mAECA</protein> was generated from <cell_type>peripheral blood lymphocytes</cell_type> of a patient with Takayasu arteritis , using Epstein-Barr virus transformation .


Activity against macrovascular EC ( HUVEC ) and microvascular EC ( human bone marrow EC immortalized by SV40 ) antigens was detected by enzyme-linked immunosorbent assay .

Activity against <cell_line>macrovascular EC</cell_line> ( <cell_line>HUVEC</cell_line> ) and <cell_line>microvascular EC</cell_line> ( <cell_line>human bone marrow EC immortalized by SV40</cell_line> ) antigens was detected by enzyme-linked immunosorbent assay .


Inhibition studies were used to select the monoclonal antibodies ( mAECA ) which share the same EC epitope binding specificity as the total IgG-AECA from the Takayasu arteritis patient .

Inhibition studies were used to select the <protein>monoclonal antibodies</protein> ( <protein>mAECA</protein> ) which share the same EC epitope binding specificity as the <protein>total IgG-AECA</protein> from the Takayasu arteritis patient .


The binding of the mAECA to human aortic EC was studied by immunohistochemistry .

The binding of the <protein>mAECA</protein> to <cell_type>human aortic EC</cell_type> was studied by immunohistochemistry .


The secretion levels of interleukin-6 ( IL-6 ) and von Willebrand factor ( vWF ) were determined , to serve as markers for EC activation .

The secretion levels of <protein>interleukin-6</protein> ( <protein>IL-6</protein> ) and von Willebrand factor ( vWF ) were determined , to serve as markers for EC activation .


The activated EC were examined for the adherence of a monocytic cell line ( U937 ) , as well as for expression of vascular cell adhesion molecule 1 , intercellular adhesion molecule 1 , and E-selectin .

The <cell_line>activated EC</cell_line> were examined for the adherence of a <cell_line>monocytic cell line</cell_line> ( <cell_line>U937</cell_line> ) , as well as for expression of <protein>vascular cell adhesion molecule 1</protein> , intercellular adhesion molecule 1 , and <protein>E-selectin</protein> .


In addition , nuclear extracts of the mAECA-treated EC were analyzed for the induction of translocation of nuclear factor kappaB ( NF-kappaB ) , using a specific NF-kappaB oligoprobe in an electrophoretic mobility shift assay .

In addition , nuclear extracts of the <cell_line>mAECA-treated EC</cell_line> were analyzed for the induction of translocation of <protein>nuclear factor kappaB</protein> ( <protein>NF-kappaB</protein> ) , using a specific <protein>NF-kappaB</protein> oligoprobe in an electrophoretic mobility shift assay .


RESULTS : Six mAECA were selected , the mixture of which produced 100 % inhibition of binding of the original IgG ( from the patient with Takayasu arteritis ) to HUVEC .

RESULTS : Six <protein>mAECA</protein> were selected , the mixture of which produced 100 % inhibition of binding of the original <protein>IgG</protein> ( from the patient with Takayasu arteritis ) to <cell_line>HUVEC</cell_line> .


All mAECA possessed high activity against macrovascular EC , but none had significant antimicrovascular EC activity .

All <protein>mAECA</protein> possessed high activity against <cell_line>macrovascular EC</cell_line> , but none had significant antimicrovascular EC activity .


The mAECA , but not normal human IgG , had anti-human aortic EC activity .

The <protein>mAECA</protein> , but not <protein>normal human IgG</protein> , had anti-human aortic EC activity .


Four of the 6 mAECA activated EC , manifested by increased IL-6 and vWF secretion .

Four of the 6 <protein>mAECA</protein> <cell_line>activated EC</cell_line> , manifested by increased <protein>IL-6</protein> and vWF secretion .


The 4 mAECA induced EC expression of adhesion molecules and increased adhesion of U937 monocytic cells to EC .

The 4 <protein>mAECA</protein> induced EC expression of <protein>adhesion molecules</protein> and increased adhesion of <cell_type>U937 monocytic cells</cell_type> to <cell_type>EC</cell_type> .


In addition , these mAECA stimulated the nuclear translocation of the NF-kappaB transcription factor .

In addition , these <protein>mAECA</protein> stimulated the nuclear translocation of the <protein>NF-kappaB transcription factor</protein> .


CONCLUSION : Our findings suggest that AECA may directly stimulate EC in Takayasu arteritis through elevation of adhesion molecule expression associated with NF-kappaB activation and adhesion of monocytes , and may therefore play a pathogenic role in the development of the vasculopathy in Takayasu arteritis .

CONCLUSION : Our findings suggest that <protein>AECA</protein> may directly stimulate <cell_type>EC</cell_type> in Takayasu arteritis through elevation of <protein>adhesion molecule</protein> expression associated with <protein>NF-kappaB</protein> activation and adhesion of <cell_type>monocytes</cell_type> , and may therefore play a pathogenic role in the development of the vasculopathy in Takayasu arteritis .


Cutting edge : expression of the NF of activated T cells in eosinophils : regulation by IL-4 and IL-5 .

Cutting edge : expression of the <protein>NF of activated T cells</protein> in <cell_type>eosinophils</cell_type> : regulation by <protein>IL-4</protein> and <protein>IL-5</protein> .


We report that NF-AT1 and NF-AT4 are expressed cytoplasmically in resting eosinophils , whereas NF-AT2 and NF-AT3 have not been seen .

We report that <protein>NF-AT1</protein> and <protein>NF-AT4</protein> are expressed cytoplasmically in <cell_type>resting eosinophils</cell_type> , whereas <protein>NF-AT2</protein> and <protein>NF-AT3</protein> have not been seen .


Likewise , NF-AT1 mRNA and NF-AT4 mRNA have been detected in resting eosinophils , and their levels can be significantly up-regulated by the Th2-associated cytokines IL-4 and IL-5 .

Likewise , <rna>NF-AT1 mRNA</rna> and <rna>NF-AT4 mRNA</rna> have been detected in <cell_type>resting eosinophils</cell_type> , and their levels can be significantly up-regulated by the <protein>Th2-associated cytokines</protein> <protein>IL-4</protein> and <protein>IL-5</protein> .


There is no detectable NF-AT protein expression in the nuclei of resting eosinophils .

There is no detectable <protein>NF-AT</protein> protein expression in the nuclei of <cell_type>resting eosinophils</cell_type> .


However NF-ATs appear in the nuclei of IL-4- , IL-5- , or ionomycin-stimulated eosinophils .

However <protein>NF-ATs</protein> appear in the nuclei of <cell_line>IL-4- , IL-5- , or ionomycin-stimulated eosinophils</cell_line> .


Only NF-AT1 and NF-AT4 , but not NF-AT2 and NF-AT3 , have translocated into the nuclei in IL-4- or IL-5-stimulated eosinophils .

Only <protein>NF-AT1</protein> and <protein>NF-AT4</protein> , but not <protein>NF-AT2</protein> and <protein>NF-AT3</protein> , have translocated into the nuclei in <cell_line>IL-4- or IL-5-stimulated eosinophils</cell_line> .


These findings delineate a novel pathway in the cytokine network in which Th2 lymphocytes `` control '' eosinophils via the release of IL-4 and IL-5 , and activation of NF-AT in eosinophils .

These findings delineate a novel pathway in the cytokine network in which <cell_line>Th2 lymphocytes</cell_line> `` control '' <cell_type>eosinophils</cell_type> via the release of <protein>IL-4</protein> and <protein>IL-5</protein> , and activation of <protein>NF-AT</protein> in <cell_type>eosinophils</cell_type> .


The findings also suggest that a later feedback `` talking '' may exist between eosinophils and Th2 lymphocytes .

The findings also suggest that a later feedback `` talking '' may exist between <cell_type>eosinophils</cell_type> and <cell_line>Th2 lymphocytes</cell_line> .


PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells .

PPARalpha activators inhibit cytokine-induced <protein>vascular cell adhesion molecule-1</protein> expression in <cell_type>human endothelial cells</cell_type> .


BACKGROUND : Adhesion molecule expression on the endothelial cell ( EC ) surface is critical for leukocyte recruitment to atherosclerotic lesions .


Better understanding of transcriptional regulation of adhesion molecules in ECs may provide important insight into plaque formation .

Better understanding of transcriptional regulation of <protein>adhesion molecules</protein> in <cell_type>ECs</cell_type> may provide important insight into plaque formation .


Peroxisome proliferator-activated receptor-alpha ( PPARalpha ) , a member of the nuclear receptor family , regulates gene expression in response to certain fatty acids and fibric acid derivatives .

<protein>Peroxisome proliferator-activated receptor-alpha</protein> ( <protein>PPARalpha</protein> ) , a member of the <protein>nuclear receptor family</protein> , regulates gene expression in response to certain fatty acids and fibric acid derivatives .


The present study investigated PPARalpha expression in human ECs and their regulation of vascular cell adhesion molecule-1 ( VCAM-1 ) .

The present study investigated <protein>PPARalpha</protein> expression in <cell_type>human ECs</cell_type> and their regulation of <protein>vascular cell adhesion molecule-1</protein> ( <protein>VCAM-1</protein> ) .


METHODS AND RESULTS : Immunohistochemistry revealed that human carotid artery ECs express PPARalpha .

METHODS AND RESULTS : Immunohistochemistry revealed that <cell_type>human carotid artery ECs</cell_type> express <protein>PPARalpha</protein> .


Pretreatment of cultured human ECs with the PPARalpha activators fenofibrate or WY14643 inhibited TNF-alpha-induced VCAM-1 in a time- and concentration-dependent manner , an effect not seen with PPARgamma activators .

Pretreatment of <cell_type>cultured human ECs</cell_type> with the <protein>PPARalpha</protein> activators fenofibrate or WY14643 inhibited <protein>TNF-alpha-induced VCAM-1</protein> in a time- and concentration-dependent manner , an effect not seen with <protein>PPARgamma</protein> activators .


Both PPARalpha activators decreased cytokine-induced VCAM-1 mRNA expression without altering its mRNA half-life .

Both <protein>PPARalpha</protein> activators decreased cytokine-induced <protein>VCAM-1</protein> mRNA expression without altering its mRNA half-life .


Transient transfection of deletional VCAM-1 promoter constructs and electrophoretic mobility shift assays suggest that fenofibrate inhibits VCAM-1 transcription in part by inhibiting NF-kappaB .

Transient transfection of deletional <dna>VCAM-1 promoter constructs</dna> and electrophoretic mobility shift assays suggest that fenofibrate inhibits <protein>VCAM-1</protein> transcription in part by inhibiting <protein>NF-kappaB</protein> .


Finally , PPARalpha activators significantly reduced adhesion of U937 cells to cultured human ECs .

Finally , <protein>PPARalpha</protein> activators significantly reduced adhesion of <cell_line>U937 cells</cell_line> to <cell_type>cultured human ECs</cell_type> .


CONCLUSIONS : Human ECs express PPARalpha , a potentially important regulator of atherogenesis through its transcriptional control of VCAM-1 gene expression .

CONCLUSIONS : <cell_type>Human ECs</cell_type> express <protein>PPARalpha</protein> , a potentially important regulator of atherogenesis through its transcriptional control of <protein>VCAM-1</protein> gene expression .


Such findings also have implications regarding the clinical use of lipid-lowering agents , like fibric acids , which can activate PPARalpha .

Such findings also have implications regarding the clinical use of lipid-lowering agents , like fibric acids , which can activate <protein>PPARalpha</protein> .


CBP/p300 integrates Raf / Rac -signaling pathways in the transcriptional induction of NF-ATc during T cell activation .

<protein>CBP/p300</protein> integrates <protein>Raf</protein> / <protein>Rac</protein> -signaling pathways in the transcriptional induction of <protein>NF-ATc</protein> during T cell activation .


NF-ATc , an inducibly expressed transcription factor , controls gene expression in T lymphocytes and cardiomyocytes .

<protein>NF-ATc</protein> , an inducibly expressed <protein>transcription factor</protein> , controls gene expression in <cell_type>T lymphocytes</cell_type> and <cell_type>cardiomyocytes</cell_type> .


We show here that the transcriptional co-activators CBP/p300 bind to and control the activity of the inducible N-terminal transactivation domain of NF-ATc , TAD-A .

We show here that the <protein>transcriptional co-activators</protein> <protein>CBP/p300</protein> bind to and control the activity of the <protein>inducible N-terminal transactivation domain</protein> of <protein>NF-ATc</protein> , <protein>TAD-A</protein> .


Similar to the N terminal transactivation domain of c-Jun , TAD-A is inducibly phosphorylated , but this phosphorylation is dispensable for the interaction with CBP/p300 .

Similar to the <protein>N terminal transactivation domain</protein> of <protein>c-Jun</protein> , <protein>TAD-A</protein> is inducibly phosphorylated , but this phosphorylation is dispensable for the interaction with <protein>CBP/p300</protein> .


Constitutive active versions of c-Raf and Rac synergistically enhance the CBP/p300 -mediated increase of TAD-A activity , indicating the important role CBP/p300 plays in the integration of T cell activation signals .

Constitutive active versions of <protein>c-Raf</protein> and <protein>Rac</protein> synergistically enhance the <protein>CBP/p300</protein> -mediated increase of <protein>TAD-A</protein> activity , indicating the important role <protein>CBP/p300</protein> plays in the integration of T cell activation signals .


Since a mutation of CBP abolishing HAT activity is almost as active as wild-type CBP in T cells , functions of CBP/p300 other than histone acetylation appear to control the NF-AT -dependent transcription in T cells .

Since a mutation of <protein>CBP</protein> abolishing HAT activity is almost as active as <protein>wild-type CBP</protein> in <cell_type>T cells</cell_type> , functions of <protein>CBP/p300</protein> other than histone acetylation appear to control the <protein>NF-AT</protein> -dependent transcription in <cell_type>T cells</cell_type> .


Immune functions , clinical parameters and hormone receptor status in breast cancer patients .


We have carried out a detailed analysis of the cellular immune functions of breast cancer patients in comparison with healthy controls .


A possible correlation between immune and clinical parameters was analysed in 50 breast cancer patients .


Immune parameters , natural killer cell and T lymphocyte functions and the numbers of circulating T lymphocytes were analysed against the clinical parameters comprising the tumour burden , the stage of the disease and the expression of hormone receptors on the tumour .

Immune parameters , <cell_type>natural killer cell</cell_type> and T lymphocyte functions and the numbers of <cell_type>circulating T lymphocytes</cell_type> were analysed against the clinical parameters comprising the tumour burden , the stage of the disease and the expression of <protein>hormone receptors</protein> on the tumour .


In order to analyse the immune function data effectively , low responders were identified with stringent cut-off values .


Considerably higher proportions of low responders were found among the patient population .


Elevated numbers of circulating T lymphocytes and CD3 -directed cytolysis correlated with the expression of oestrogen receptors independently of the clinical/histological parameters .

Elevated numbers of <cell_type>circulating T lymphocytes</cell_type> and <protein>CD3</protein> -directed cytolysis correlated with the expression of <protein>oestrogen receptors</protein> independently of the clinical/histological parameters .


Latent membrane protein 1 of Epstein-Barr virus interacts with JAK3 and activates STAT proteins .

<protein>Latent membrane protein 1</protein> of Epstein-Barr virus interacts with <protein>JAK3</protein> and activates <protein>STAT proteins</protein> .


Latent membrane protein 1 ( LMP1 ) acts like a permanently activated receptor of the tumor necrosis factor ( TNF ) -receptor superfamily and is absolutely required for B cell immortalization by Epstein-Barr virus .

<protein>Latent membrane protein 1</protein> ( <protein>LMP1</protein> ) acts like a <protein>permanently activated receptor</protein> of the <protein>tumor necrosis factor ( TNF ) -receptor superfamily</protein> and is absolutely required for B cell immortalization by Epstein-Barr virus .


Molecular and biochemical approaches demonstrated that LMP1 usurps cellular signaling pathways resulting in the induction of NF-kappaB and AP-1 via two C-terminal activating regions .

Molecular and biochemical approaches demonstrated that <protein>LMP1</protein> usurps cellular signaling pathways resulting in the induction of <protein>NF-kappaB</protein> and <protein>AP-1</protein> via two <protein>C-terminal activating regions</protein> .


We demonstrate here that a third region encompassing a proline rich sequence within the 33 bp repetitive stretch of LMP1 's C-terminus is required for the activation of Janus kinase 3 ( JAK3 ) .

We demonstrate here that a third region encompassing a <protein>proline rich sequence</protein> within the 33 bp repetitive stretch of <protein>LMP1</protein> 's <protein>C-terminus</protein> is required for the activation of <protein>Janus kinase 3</protein> ( <protein>JAK3</protein> ) .


The interaction of LMP1 and JAK3 leads to the enhanced tyrosine auto/transphosphorylation of JAK3 within minutes after crosslinking of a conditional NGF-R : LMP1 chimera and is a prerequisite for the activation of STAT transcription factors .

The interaction of <protein>LMP1</protein> and <protein>JAK3</protein> leads to the enhanced tyrosine auto/transphosphorylation of <protein>JAK3</protein> within minutes after crosslinking of a conditional <protein>NGF-R : LMP1 chimera</protein> and is a prerequisite for the activation of <protein>STAT transcription factors</protein> .


These results reveal a novel activating region in the LMP1 C-terminus and identify the JAK /STAT pathway as a target of this viral integral membrane protein in B cells .

These results reveal a novel activating region in the <protein>LMP1</protein> <protein>C-terminus</protein> and identify the <protein>JAK</protein> <protein>/STAT</protein> pathway as a target of this <protein>viral integral membrane protein</protein> in <cell_type>B cells</cell_type> .


Monocyte arrest and transmigration on inflamed endothelium in shear flow is inhibited by adenovirus-mediated gene transfer of IkappaB-alpha .

Monocyte arrest and transmigration on inflamed endothelium in shear flow is inhibited by adenovirus-mediated gene transfer of <protein>IkappaB-alpha</protein> .


Mobilization of nuclear factor-kappaB ( NF-kappaB ) activates transcription of genes encoding endothelial adhesion molecules and chemokines that contribute to monocyte infiltration critical in atherogenesis .

Mobilization of <protein>nuclear factor-kappaB</protein> ( <protein>NF-kappaB</protein> ) activates transcription of genes encoding <protein>endothelial adhesion molecules</protein> and chemokines that contribute to monocyte infiltration critical in atherogenesis .


Inhibition of NF-kappaB has been achieved by pharmacological and genetic approaches ; however , monocyte interactions with activated endothelium in shear flow following gene transfer of the NF-kappaB inhibitor IkappaB-alpha have not been studied .

Inhibition of <protein>NF-kappaB</protein> has been achieved by pharmacological and genetic approaches ; however , monocyte interactions with activated endothelium in shear flow following gene transfer of the <protein>NF-kappaB</protein> inhibitor <protein>IkappaB-alpha</protein> have not been studied .


We found that overexpression of IkappaB-alpha in endothelial cells using a recombinant adenovirus prevented tumor necrosis factor-alpha ( TNF-alpha ) -induced degradation of IkappaB-alpha and suppressed the upregulation of vascular cell adhesion molecule-1 ( VCAM-1 ) , intercellular adhesion molecule-1 ( ICAM-1 ) , and E-selectin mRNA and surface protein expression and the upregulation of transcripts for the chemokines monocyte chemoattractant protein 1 ( MCP-1 ) and growth-related activity-alpha ( GRO-alpha ) by TNF-alpha .

We found that overexpression of <protein>IkappaB-alpha</protein> in <cell_type>endothelial cells</cell_type> using a recombinant adenovirus prevented <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) -induced degradation of <protein>IkappaB-alpha</protein> and suppressed the upregulation of <protein>vascular cell adhesion molecule-1</protein> ( <protein>VCAM-1</protein> ) , <protein>intercellular adhesion molecule-1</protein> ( <protein>ICAM-1</protein> ) , and <rna>E-selectin mRNA</rna> and surface protein expression and the upregulation of transcripts for the <protein>chemokines</protein> <protein>monocyte chemoattractant protein 1</protein> ( <protein>MCP-1</protein> ) and <protein>growth-related activity-alpha</protein> ( <protein>GRO-alpha</protein> ) by <protein>TNF-alpha</protein> .


This was associated with a reduction in endothelial MCP-1 secretion and GRO-alpha immobilization .

This was associated with a reduction in endothelial <protein>MCP-1</protein> secretion and <protein>GRO-alpha</protein> immobilization .


Adhesion assays under physiological shear flow conditions showed that firm arrest , spreading , and transmigration of monocytes on TNF-alpha -activated endothelium was markedly inhibited by IkappaB-alpha overexpression .

Adhesion assays under physiological shear flow conditions showed that firm arrest , spreading , and transmigration of <cell_type>monocytes</cell_type> on <protein>TNF-alpha</protein> -activated endothelium was markedly inhibited by <protein>IkappaB-alpha</protein> overexpression .


Inhibition with monoclonal antibodies and peptide antagonists inferred that this was due to reduced expression of Ig integrin ligand as well as of chemokines specifically involved in these events .

Inhibition with <protein>monoclonal antibodies</protein> and peptide antagonists inferred that this was due to reduced expression of Ig integrin ligand as well as of <protein>chemokines</protein> specifically involved in these events .


In contrast , rolling of monocytes was increased by IkappaB-alpha transfer and was partly mediated by P-selectin ; however , it appeared to be unaffected by the inhibition of E-selectin induction .

In contrast , rolling of <cell_type>monocytes</cell_type> was increased by <protein>IkappaB-alpha</protein> transfer and was partly mediated by <protein>P-selectin</protein> ; however , it appeared to be unaffected by the inhibition of <protein>E-selectin</protein> induction .


Thus , our data provide novel evidence that selective modulation of NF-kappaB by adenoviral transfer of IkappaB-alpha impairs the expression of multiple endothelial gene products required for subsequent monocyte arrest and emigration in shear flow and thus for monocyte infiltration in atherosclerotic plaques .

Thus , our data provide novel evidence that selective modulation of <protein>NF-kappaB</protein> by adenoviral transfer of <protein>IkappaB-alpha</protein> impairs the expression of multiple <protein>endothelial gene products</protein> required for subsequent monocyte arrest and emigration in shear flow and thus for monocyte infiltration in atherosclerotic plaques .


Recognition of NFATp/AP-1 composite elements within genes induced upon the activation of immune cells .

Recognition of <dna>NFATp/AP-1 composite elements</dna> within genes induced upon the activation of <cell_type>immune cells</cell_type> .


Composite elements are regulatory modules of promoters or enhancers that consist of binding sites of two different but synergizing transcription factors .

<dna>Composite elements</dna> are <dna>regulatory modules</dna> of <dna>promoters</dna> or <dna>enhancers</dna> that consist of binding sites of two different but synergizing <protein>transcription factors</protein> .


A well-studied example is nuclear factors of activated T-cell ( NFAT ) sites which are composite elements of a NFATp/c and an activating protein 1 ( AP-1 ) binding site .

A well-studied example is <dna>nuclear factors of activated T-cell ( NFAT ) sites</dna> which are composite elements of a <dna>NFATp/c and an activating protein 1 ( AP-1 ) binding site</dna> .


We have developed a computational approach to identify potential NFAT target genes which ( a ) comprises an improved method to scan for individual NFAT composite elements ; ( b ) considers positional effects relative to transcription start sites ; and ( c ) involves cluster analysis of potential NFAT composite elements .

We have developed a computational approach to identify potential <dna>NFAT target genes</dna> which ( a ) comprises an improved method to scan for individual <dna>NFAT composite elements</dna> ; ( b ) considers positional effects relative to <dna>transcription start sites</dna> ; and ( c ) involves cluster analysis of potential <dna>NFAT composite elements</dna> .


All three steps progressively helpX ? ed to discriminate T-cell-specific promoter sequences against other functional regions ( coding and intronic sequences ) of the same genes , against promoters of muscle-specific genes or against random sequences .

All three steps progressively helpX ? ed to discriminate <dna>T-cell-specific promoter sequences</dna> against other <dna>functional regions</dna> ( <dna>coding and intronic sequences</dna> ) of the same genes , against <dna>promoters</dna> of <dna>muscle-specific genes</dna> or against <dna>random sequences</dna> .


Using this approach , we identified potential NFAT composite elements in promoters of cytokine genes and their receptors as well as in promoters of genes for AP-1 family members , Ca2+-binding proteins and some other components of the regulatory network operating in activated T-cells and other immune cells .

Using this approach , we identified potential <dna>NFAT composite elements</dna> in <dna>promoters</dna> of <dna>cytokine genes</dna> and their receptors as well as in <dna>promoters</dna> of genes for <protein>AP-1 family members</protein> , <protein>Ca2+-binding proteins</protein> and some other components of the regulatory network operating in <cell_type>activated T-cells</cell_type> and other <cell_type>immune cells</cell_type> .


The method developed can be adapted to characterize and identify other composite elements as well .

The method developed can be adapted to characterize and identify other <dna>composite elements</dna> as well .


The program for recognition NFAT composite elements is available through the World Wide Web ( http : //compel.bionet.nsc.ru/FunSite/CompelScan.html and http : //transfac.gbf.de/dbsearch/funsitep/s_comp.html ) .

The program for recognition <dna>NFAT composite elements</dna> is available through the World Wide Web ( http : //compel.bionet.nsc.ru/FunSite/CompelScan.html and http : //transfac.gbf.de/dbsearch/funsitep/s_comp.html ) .


Copyright 1999 Academic Press .


The oestrogen receptor codon 10 polymorphism detected in breast cancer is also present in non-malignant cells .

The <protein>oestrogen receptor</protein> <dna>codon 10</dna> polymorphism detected in breast cancer is also present in <cell_type>non-malignant cells</cell_type> .


The effect of oestrogens on oestrogen-receptive organs and cells is mediated via intracellular receptors ( ERalpha and ERbeta ) .

The effect of oestrogens on oestrogen-receptive organs and cells is mediated via <protein>intracellular receptors</protein> ( <protein>ERalpha</protein> and <protein>ERbeta</protein> ) .


Oestrogen receptor gene polymorphisms in the region encoding the N-terminal portion of the protein are reportedly associated with pathological conditions including breast cancer , hypertension , spontaneous abortion and coronary heart disease .

<protein>Oestrogen receptor</protein> gene polymorphisms in the region encoding the <protein>N-terminal portion</protein> of the protein are reportedly associated with pathological conditions including breast cancer , hypertension , spontaneous abortion and coronary heart disease .


A silent mutation in codon 10 of exon 1 , detected in ER-negative and ER-positive human breast cancer cell lines , in breast tumors and blood DNA from breast cancer patients , has been recognized as a polymorphic site .

A silent mutation in <dna>codon 10</dna> of <dna>exon 1</dna> , detected in <cell_line>ER-negative and ER-positive human breast cancer cell lines</cell_line> , in breast tumors and <dna>blood DNA</dna> from breast cancer patients , has been recognized as a <dna>polymorphic site</dna> .


In this study we examined , by denaturing gradient-gel electrophoresis and DNA sequence analysis , the possible presence of a codon 10 polymorphic site in normal oestrogen target organs and cells such as the uterus ( myometrium and endometrium ) , in the placenta and peripheral blood mononuclear cells and in a benign uterus tumour ( leiomyoma ) .

In this study we examined , by denaturing gradient-gel electrophoresis and <dna>DNA sequence</dna> analysis , the possible presence of a <dna>codon 10 polymorphic site</dna> in normal oestrogen target organs and cells such as the uterus ( myometrium and endometrium ) , in the placenta and <cell_type>peripheral blood mononuclear cells</cell_type> and in a benign uterus tumour ( leiomyoma ) .


We have detected ER codon 10 polymorphism in these samples and have compared them to those observed in breast cancer samples .

We have detected <dna>ER codon 10</dna> polymorphism in these samples and have compared them to those observed in breast cancer samples .


All tissues and cells studied were homozygous for the wild-type gene , and were heterozygous as well as homozygous for the codon-10-variant type .

All tissues and cells studied were homozygous for the <dna>wild-type gene</dna> , and were heterozygous as well as homozygous for the <dna>codon-10-variant type</dna> .


These results indicate that the presence of the codon-10-variant type is not a characteristic of breast cancer .

These results indicate that the presence of the <dna>codon-10-variant type</dna> is not a characteristic of breast cancer .


Out current findings suggest that further investigations are warranted to elucidate the possible linkage of ER codon 10 polymorphism to physiological and pathological conditions .

Out current findings suggest that further investigations are warranted to elucidate the possible linkage of <dna>ER codon 10</dna> polymorphism to physiological and pathological conditions .


USF/c-Myc enhances , while Yin-Yang 1 suppresses , the promoter activity of CXCR4 , a coreceptor for HIV-1 entry .

<protein>USF/c-Myc</protein> enhances , while <protein>Yin-Yang 1</protein> suppresses , the promoter activity of <protein>CXCR4</protein> , a <protein>coreceptor</protein> for HIV-1 entry .


Transcription factors USF1 and USF2 up-regulate gene expression ( i.e. , HIV-1 long terminal repeats ) via interaction with an E box on their target promoters , which is also a binding site for c-Myc .

<protein>Transcription factors</protein> <protein>USF1</protein> and <protein>USF2</protein> up-regulate gene expression ( i.e. , <dna>HIV-1 long terminal repeats</dna> ) via interaction with an <dna>E box</dna> on their target promoters , which is also a <dna>binding site</dna> for <protein>c-Myc</protein> .


The c-Myc oncoprotein is important in control of cellular proliferation and differentiation , while Yin-Yang 1 ( YY1 ) has been shown to control the expression of a number of cellular and viral genes .

The <protein>c-Myc oncoprotein</protein> is important in control of cellular proliferation and differentiation , while <protein>Yin-Yang 1</protein> ( <protein>YY1</protein> ) has been shown to control the expression of a number of <dna>cellular and viral genes</dna> .


These two proteins physically interact with each other and mutually inhibit their respective biological functions .


In this study , we show that USF/c-Myc up-regulates , while YY1 down-regulates the promoter activity of CXCR4 , a coreceptor for T cell-tropic HIV-1 entry .

In this study , we show that <protein>USF/c-Myc</protein> up-regulates , while <protein>YY1</protein> down-regulates the promoter activity of <protein>CXCR4</protein> , a coreceptor for T cell-tropic HIV-1 entry .


We have identified an E box around -260 and a YY1 binding site around -300 relative to the transcription start site .

We have identified an <dna>E box</dna> around <dna>-260</dna> and a <dna>YY1 binding site</dna> around <dna>-300</dna> relative to the <dna>transcription start site</dna> .


Mutation of the E box abolished USF/c-Myc -mediated up-regulation of CXCR4 promoter activity , and mutation of the YY1 binding site was associated with unresponsiveness to YY1 -mediated inhibition .

Mutation of the <dna>E box</dna> abolished <protein>USF/c-Myc</protein> -mediated up-regulation of <protein>CXCR4</protein> promoter activity , and mutation of the <dna>YY1 binding site</dna> was associated with unresponsiveness to <protein>YY1</protein> -mediated inhibition .


These data suggest that USF/c-Myc and YY1 may play an important role in the HIV-1-replicative cycle , by modulating both the viral fusion/entry process and viral expression .

These data suggest that <protein>USF/c-Myc</protein> and <protein>YY1</protein> may play an important role in the HIV-1-replicative cycle , by modulating both the viral fusion/entry process and viral expression .


Suppression of NF-kappaB activation in normal T cells by supernatant fluid from human renal cell carcinomas .

Suppression of <protein>NF-kappaB</protein> activation in <cell_type>normal T cells</cell_type> by supernatant fluid from human renal cell carcinomas .


T lymphocytes from patients with renal cell carcinoma ( RCC ) show reduced immune function and impaired activation of the transcription factor , NF-kappaB .

<cell_type>T lymphocytes</cell_type> from patients with renal cell carcinoma ( RCC ) show reduced immune function and impaired activation of the <protein>transcription factor</protein> , <protein>NF-kappaB</protein> .


We determined the mechanism of NF-kappaB suppression in T cells of RCC patient and determined whether supernatant fluid from RCC explants ( RCC-S ) induced the same phenotype of NF-kappaB suppression in normal T cells that is observed in patient T cells .

We determined the mechanism of <protein>NF-kappaB</protein> suppression in <cell_type>T cells</cell_type> of RCC patient and determined whether supernatant fluid from RCC explants ( RCC-S ) induced the same phenotype of <protein>NF-kappaB</protein> suppression in <cell_type>normal T cells</cell_type> that is observed in patient <cell_type>T cells</cell_type> .


The pattern of kappaB -binding activity in T cells of RCC patient was altered as compared to that seen in T cells obtained from normal volunteers .

The pattern of <protein>kappaB</protein> -binding activity in <cell_type>T cells</cell_type> of RCC patient was altered as compared to that seen in <cell_type>T cells</cell_type> obtained from normal volunteers .


In some patients , no activation of RelA/NFkappaB1 -binding activity was detectable , while in others kappaB -binding activity was modestly induced but the duration was reduced .

In some patients , no activation of <protein>RelA/NFkappaB1</protein> -binding activity was detectable , while in others <protein>kappaB</protein> -binding activity was modestly induced but the duration was reduced .


IkappaBalpha was degraded normally following stimulation in both normal controls and T cells from RCC patients .

<protein>IkappaBalpha</protein> was degraded normally following stimulation in both normal controls and <cell_type>T cells</cell_type> from RCC patients .


RCC-S did not alter the cytoplasmic levels of RelA and NF-kappaB1 but did suppress their nuclear localization and inhibited the activation of RelA/NF-kappaB1 binding complexes .

RCC-S did not alter the cytoplasmic levels of <protein>RelA</protein> and <protein>NF-kappaB1</protein> but did suppress their nuclear localization and inhibited the activation of <protein>RelA/NF-kappaB1 binding complexes</protein> .


These results show that RCC-S can induce in normal T cells the same phenotype of impaired NF-kappaB activation that is detected in T cells of RCC patient .

These results show that RCC-S can induce in <cell_type>normal T cells</cell_type> the same phenotype of impaired <protein>NF-kappaB</protein> activation that is detected in <cell_type>T cells</cell_type> of RCC patient .


It also appears that NF-kappaB suppression by RCC-S may contribute to the immunosuppression of host immunity .

It also appears that <protein>NF-kappaB</protein> suppression by RCC-S may contribute to the immunosuppression of host immunity .


STAT1 activation during monocyte to macrophage maturation : role of adhesion molecules .

<protein>STAT1</protein> activation during monocyte to macrophage maturation : role of <protein>adhesion molecules</protein> .


Human monocytes isolated from peripheral blood of healthy donors show a time-dependent differentiation into macrophages upon in vitro cultivation , closely mimicking their in vivo migration and maturation into extravascular tissues .

<cell_type>Human monocytes</cell_type> isolated from peripheral blood of healthy donors show a time-dependent differentiation into <cell_type>macrophages</cell_type> upon in vitro cultivation , closely mimicking their in vivo migration and maturation into extravascular tissues .


The mediator ( s ) of this maturation process has not been yet defined .


We investigated the involvement of signal transducers and activators of transcription ( STAT ) factors in this phenomenon and reported the specific , time-dependent , activation of STAT1 protein starting at day 0/1 of cultivation and maximally expressed at day 5 .

We investigated the involvement of <protein>signal transducers and activators of transcription ( STAT ) factors</protein> in this phenomenon and reported the specific , time-dependent , activation of <protein>STAT1</protein> protein starting at day 0/1 of cultivation and maximally expressed at day 5 .


STAT1 activity was evident on the STAT binding sequences ( SBE ) present in the promoters of genes which are up-regulated during monocyte to macrophage maturation such as FcgammaRI and ICAM-1 , and in the promoter of the transcription factor IFN regulatory factor-1 .

<protein>STAT1</protein> activity was evident on the <dna>STAT binding sequences</dna> ( <dna>SBE</dna> ) present in the <dna>promoters</dna> of genes which are up-regulated during monocyte to macrophage maturation such as <dna>FcgammaRI</dna> and <dna>ICAM-1</dna> , and in the promoter of the <dna>transcription factor IFN regulatory factor-1</dna> .


Moreover , the effect of cell adhesion to fibronectin or laminin was studied to investigate mechanisms involved in STAT1 activation .

Moreover , the effect of cell adhesion to fibronectin or laminin was studied to investigate mechanisms involved in <protein>STAT1</protein> activation .


Compared with monocytes adherent on plastic surfaces , freshly isolated cells allowed to adhere either to fibronectin- or laminin-coated flasks exhibited an increased STAT1 binding activity both in control and in IFN-gamma-treated cells .

Compared with <cell_type>monocytes</cell_type> adherent on plastic surfaces , freshly isolated cells allowed to adhere either to fibronectin- or laminin-coated flasks exhibited an increased <protein>STAT1</protein> binding activity both in control and in <cell_line>IFN-gamma-treated cells</cell_line> .


The molecular events leading to enhanced STAT1 activation and cytokine responsiveness concerned both Y701 and S727 STAT1 phosphorylation .

The molecular events leading to enhanced <protein>STAT1</protein> activation and <protein>cytokine</protein> responsiveness concerned both <protein>Y701</protein> and <protein>S727 STAT1</protein> phosphorylation .


Exogenous addition of transforming growth factor-beta , which exerts an inhibitory effect on some monocytic differentiation markers , inhibited macrophage maturation , integrin expression and STAT1 binding activity .

Exogenous addition of <protein>transforming growth factor-beta</protein> , which exerts an inhibitory effect on some <protein>monocytic differentiation markers</protein> , inhibited macrophage maturation , integrin expression and <protein>STAT1</protein> binding activity .


Taken together these results indicate that STAT1 plays a pivotal role in the differentiation/maturation process of monocytes as an early transcription factor initially activated by adherence and then able to modulate the expression of functional genes , such as ICAM-1 and FcgammaRI .

Taken together these results indicate that <protein>STAT1</protein> plays a pivotal role in the differentiation/maturation process of <cell_type>monocytes</cell_type> as an early <protein>transcription factor</protein> initially activated by adherence and then able to modulate the expression of <dna>functional genes</dna> , such as <protein>ICAM-1</protein> and <protein>FcgammaRI</protein> .


Expression and role of PML gene in normal adult hematopoiesis : functional interaction between PML and Rb proteins in erythropoiesis .

Expression and role of <dna>PML gene</dna> in normal adult hematopoiesis : functional interaction between <protein>PML and Rb proteins</protein> in erythropoiesis .


The expression of the PML gene was investigated in purified early hematopoietic progenitor cells ( HPCs ) induced to unilineage erythroid or granulocytic differentiation .

The expression of the <dna>PML gene</dna> was investigated in purified early <cell_type>hematopoietic progenitor cells</cell_type> ( <cell_type>HPCs</cell_type> ) induced to unilineage erythroid or granulocytic differentiation .


PML mRNA and protein , while barely detectable in quiescent HPCs , are consistently induced by growth factor stimulation through the erythroid or granulocytic lineage .

<rna>PML mRNA</rna> and <protein>protein</protein> , while barely detectable in quiescent <cell_type>HPCs</cell_type> , are consistently induced by <protein>growth factor</protein> stimulation through the erythroid or granulocytic lineage .


Thereafter , PML is downmodulated in late granulocytic maturation , whereas it is sustainably expressed through the erythroid pathway .

Thereafter , <protein>PML</protein> is downmodulated in late granulocytic maturation , whereas it is sustainably expressed through the erythroid pathway .


In functional studies , PML expression was inhibited by addition of antisense oligomers targeting PML mRNA ( alpha-PML ) .

In functional studies , <protein>PML</protein> expression was inhibited by addition of antisense oligomers targeting <rna>PML mRNA</rna> ( <protein>alpha-PML</protein> ) .


Interestingly , early treatment ( day 0 HPCs ) with alpha-PML reduced the number of both erythroid and granulocytic colonies , whereas late treatment ( day 5 culture ) reduced erythroid , but not granulocytic , clonogenesis .

Interestingly , early treatment ( day 0 <cell_type>HPCs</cell_type> ) with <protein>alpha-PML</protein> reduced the number of both <cell_line>erythroid and granulocytic colonies</cell_line> , whereas late treatment ( day 5 culture ) reduced erythroid , but not granulocytic , clonogenesis .


These findings suggest that PML is required for early hematopoiesis and erythroid , but not granulocytic maturation .

These findings suggest that <protein>PML</protein> is required for early hematopoiesis and erythroid , but not granulocytic maturation .


The pattern of PML expression in normal hematopoiesis mimics that of retinoblastoma pRb 105 .

The pattern of <protein>PML</protein> expression in normal hematopoiesis mimics that of <cell_type>retinoblastoma</cell_type> <protein>pRb 105</protein> .


Combined treatment of HPCs with alpha-PML and alpha-Rb oligomers inhibited both PML and Rb protein expression and completely blocked erythroid colony development .

Combined treatment of <cell_type>HPCs</cell_type> with <protein>alpha-PML</protein> and alpha-Rb oligomers inhibited both PML and Rb protein expression and completely blocked erythroid colony development .


Furthermore , PML and pRb 105 were co-immunoprecipitated in cellular lysates derived from erythroid precursors indicating that this functional interaction may have a biochemical basis .

Furthermore , <protein>PML</protein> and <protein>pRb 105</protein> were co-immunoprecipitated in cellular lysates derived from <cell_type>erythroid precursors</cell_type> indicating that this functional interaction may have a biochemical basis .


These results suggest a key functional role of PML in early hematopoiesis and late erythropoiesis : the latter phenomenon may be related to the molecular and functional interaction of PML with pRb 105 .

These results suggest a key functional role of <protein>PML</protein> in early hematopoiesis and late erythropoiesis : the latter phenomenon may be related to the molecular and functional interaction of <protein>PML</protein> with <protein>pRb 105</protein> .


Binding characteristics of the glucocorticoid receptor in peripheral blood lymphocytes in multiple sclerosis .

Binding characteristics of the <protein>glucocorticoid receptor</protein> in <cell_type>peripheral blood lymphocytes</cell_type> in multiple sclerosis .


Although the exact etiology of multiple sclerosis ( MS ) remains unresolved , immune reactions are believed to be the central pathogenic mechanisms .


Endogenous and therapeutic steroid hormones affect the immune system , and inflammatory diseases are associated with activation of the hypothalamic-pituitary-adrenal axis , providing evidence of an immune-endocrine interplay .


Function tests in MS have revealed dysregulation of the hypothalamic-pituitary-adrenal system in a substantial proportion of patients .


We characterized glucocorticoid receptor ( GR ) binding in peripheral blood lymphocytes from 39 MS patients and 14 age- and sex-matched controls with respect to dissociation constant and binding capacity , using a whole-cell binding assay with [ 3H ] dexamethasone as the ligand .

We characterized <protein>glucocorticoid receptor</protein> ( <protein>GR</protein> ) binding in <cell_type>peripheral blood lymphocytes</cell_type> from 39 MS patients and 14 age- and sex-matched controls with respect to dissociation constant and binding capacity , using a whole-cell binding assay with [ 3H ] dexamethasone as the ligand .


GR binding parameters did not differ significantly between patients ( Kd 8.98 +/- 1.07 nM , Bmax 183 +/- 29.8 fmol/mg ) and controls ( Kd 9.36 +/- 1.17 nM , Bmax 158 +/- 16 fmol/mg ) .

<protein>GR</protein> binding parameters did not differ significantly between patients ( Kd 8.98 +/- 1.07 nM , Bmax 183 +/- 29.8 fmol/mg ) and controls ( Kd 9.36 +/- 1.17 nM , Bmax 158 +/- 16 fmol/mg ) .


No effect of age , sex , course , duration or severity of disease , or prior steroid treatments was detected .


GR binding parameters were analyzed in relation to the results of the combined dexamethasone -CRH test , which reflects corticosteroid receptor function at the hypothalamus , in 30 patients and 9 controls .

<protein>GR</protein> binding parameters were analyzed in relation to the results of the combined dexamethasone <protein>-CRH</protein> test , which reflects corticosteroid receptor function at the hypothalamus , in 30 patients and 9 controls .


While controls showed a moderate correlation between binding affinity of the GR in lymphocytes and regulatory function at the hypothalamic level , the patients did not .

While controls showed a moderate correlation between binding affinity of the <protein>GR</protein> in lymphocytes and regulatory function at the hypothalamic level , the patients did not .


These data suggest that the physiological relationship between binding and function of the glucocorticoid receptor is disturbed in MS .

These data suggest that the physiological relationship between binding and function of the <protein>glucocorticoid receptor</protein> is disturbed in MS .


Phorbol ester-induced mononuclear cell differentiation is blocked by the mitogen-activated protein kinase kinase ( MEK ) inhibitor PD98059 .

Phorbol ester-induced mononuclear cell differentiation is blocked by the <protein>mitogen-activated protein kinase kinase</protein> ( <protein>MEK</protein> ) inhibitor PD98059 .


The purpose of this study was to evaluate whether the mitogen-activated protein kinase ( MAPK ) signaling pathway contributes to 12-O-tetradecanoylphorbol-13-acetate ( TPA ) -induced mononuclear differentiation in the human myeloblastic leukemia ML-1 cells .

The purpose of this study was to evaluate whether the <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) signaling pathway contributes to 12-O-tetradecanoylphorbol-13-acetate ( TPA ) -induced mononuclear differentiation in the <cell_line>human myeloblastic leukemia ML-1 cells</cell_line> .