To investigate in vivo regulatory mechanisms that control the population of type 2 T cells and disease susceptibility , we have created lines of transgenic mice in which expression of a chimeric cytokine receptor ( the mouse interleukin 2 receptor beta chain [ IL-2Rbeta ] extracellular domain fused to the cytoplasmic tail of IL-4Ralpha ) is targeted to the T lymphoid lineage using the proximal lck promoter .

To investigate in vivo regulatory mechanisms that control the population of <cell_type>type 2 T cells</cell_type> and disease susceptibility , we have created lines of transgenic mice in which expression of a <protein>chimeric cytokine receptor</protein> ( the <protein>mouse interleukin 2 receptor beta chain [ IL-2Rbeta ] extracellular domain</protein> fused to the <protein>cytoplasmic tail</protein> of <protein>IL-4Ralpha</protein> ) is targeted to the <cell_type>T lymphoid lineage</cell_type> using the <dna>proximal lck promoter</dna> .


This chimera transduced IL-4 -specific signals in response to IL-2 binding and dramatically enhanced type 2 responses ( IL-4 , IL-5 , and immunoglobulin E production ) upon in vitro TCR stimulation or in vivo antigen challenge .

This chimera transduced <protein>IL-4</protein> -specific signals in response to <protein>IL-2</protein> binding and dramatically enhanced type 2 responses ( <protein>IL-4</protein> , <protein>IL-5</protein> , and <protein>immunoglobulin E</protein> production ) upon in vitro <protein>TCR</protein> stimulation or in vivo antigen challenge .


Thus , type 2 effector function was augmented by IL-4 signals transduced through a chimeric receptor expressed in a T cell-specific manner .

Thus , type 2 effector function was augmented by <protein>IL-4</protein> signals transduced through a <protein>chimeric receptor</protein> expressed in a T cell-specific manner .


This influence was sufficient for establishment of antigen-induced allergic airway hyperresponsiveness on a disease-resistant background


Differentiation-dependent expression of a human carboxylesterase in monocytic cells and transcription factor binding to the promoter .

Differentiation-dependent expression of a <protein>human carboxylesterase</protein> in <cell_type>monocytic cells</cell_type> and <protein>transcription factor</protein> binding to the <dna>promoter</dna> .


Carboxylesterases play an important role in defense and clearance mechanisms of the monocyte/macrophage system .

<protein>Carboxylesterases</protein> play an important role in defense and clearance mechanisms of the monocyte/macrophage system .


During the differentiation process of cells from the monocytic cell line THP-1 we observed a transient transcriptional upregulation of a human carboxylesterase analyzed by means of Northern blots .

During the differentiation process of cells from the <cell_line>monocytic cell line THP-1</cell_line> we observed a transient transcriptional upregulation of a <protein>human carboxylesterase</protein> analyzed by means of Northern blots .


In PMA-treated THP-1 cells we could detect three major transcription initiation sites as revealed by Nuclease Protection Assay carried out with two overlapping antisense RNA probes .

In <cell_line>PMA-treated THP-1 cells</cell_line> we could detect three major <dna>transcription initiation sites</dna> as revealed by Nuclease Protection Assay carried out with two <rna>overlapping antisense RNA probes</rna> .


We have recently cloned the carboxylesterase upstream sequence and showed its basal promoter activity in CHO cells .

We have recently cloned the <dna>carboxylesterase upstream sequence</dna> and showed its <dna>basal promoter</dna> activity in <cell_line>CHO cells</cell_line> .


Using electrophoretic mobility shift analysis we demonstrated that the promoter region spanning base pairs -1 to -275 , which contains several putative binding sites for transcription factors , is bound by nuclear factors Sp1 and IRBP but not by C/EBPs .

Using electrophoretic mobility shift analysis we demonstrated that the <dna>promoter region</dna> spanning <dna>base pairs -1 to -275</dna> , which contains several putative binding sites for <protein>transcription factors</protein> , is bound by <protein>nuclear factors</protein> <protein>Sp1</protein> and <protein>IRBP</protein> but not by <protein>C/EBPs</protein> .


Taken together these data indicate that carboxylesterase gene transcription in THP-1 cells starts at multiple initiation sites and that Sp1 and IRBP may be critical factors for modulating the differentiation-dependent transcription of this human carboxylesterase gene .

Taken together these data indicate that carboxylesterase gene transcription in <cell_line>THP-1 cells</cell_line> starts at multiple initiation sites and that <protein>Sp1</protein> and <protein>IRBP</protein> may be critical factors for modulating the differentiation-dependent transcription of this <dna>human carboxylesterase gene</dna> .


The role of the Ikaros gene in lymphocyte development and homeostasis .

The role of the <dna>Ikaros gene</dna> in lymphocyte development and homeostasis .


The Ikaros gene , which encodes a family of hemopoietic-specific zinc finger proteins , is described as a central regulator of lymphocyte differentiation .

The <dna>Ikaros gene</dna> , which encodes a family of <protein>hemopoietic-specific zinc finger proteins</protein> , is described as a central regulator of lymphocyte differentiation .


During fetal development , it is required at the earliest stage of T cell and B cell specification .


In the adult , however , lymphoid lineages rely on Ikaros at distinct phases of their development .

In the adult , however , <cell_type>lymphoid lineages</cell_type> rely on <dna>Ikaros</dna> at distinct phases of their development .


Its activity is essential for the generation of B cell but not of T cell precursors , although the differentiation of the latter is not normal .

Its activity is essential for the generation of <cell_type>B cell</cell_type> but not of <cell_type>T cell precursors</cell_type> , although the differentiation of the latter is not normal .


A significant increase in CD4 thymocytes and their immediate precursors is detected , and because these cells lack markers that correlate with positive selection , a deregulation in their maturation process is suggested .

A significant increase in <cell_type>CD4 thymocytes</cell_type> and their immediate precursors is detected , and because these cells lack markers that correlate with positive selection , a deregulation in their maturation process is suggested .


Furthermore , Ikaros-null thymocytes hyperproliferate in response to T cell receptor ( TCR ) signaling ; within days after their appearance in the thymus , clonally expanding populations are detected .

Furthermore , <cell_type>Ikaros-null thymocytes</cell_type> hyperproliferate in response to <protein>T cell receptor</protein> ( <protein>TCR</protein> ) signaling ; within days after their appearance in the thymus , clonally expanding populations are detected .


Deregulated TCR -mediated responses and the fast kinetics of tumor development in these mutant thymocytes implicate Ikaros as a central tumor suppressor gene for the T cell lineage .

Deregulated <protein>TCR</protein> -mediated responses and the fast kinetics of tumor development in these <cell_type>mutant thymocytes</cell_type> implicate Ikaros as a <dna>central tumor suppressor gene</dna> for the <cell_type>T cell lineage</cell_type> .


In addition , lack of natural killer cells and selective defects in gamma delta T cells and dendritic antigen-presenting cells point to Ikaros as an essential factor for the establishment of early branchpoints of the T cell pathway .

In addition , lack of <cell_type>natural killer cells</cell_type> and selective defects in <cell_type>gamma delta T cells</cell_type> and <cell_type>dendritic antigen-presenting cells</cell_type> point to <protein>Ikaros</protein> as an essential factor for the establishment of early branchpoints of the T cell pathway .


The dominant interference activity of Ikaros isoforms unable to bind DNA and their effects in lymphocyte development suggest that Ikaros works in concert with other factors .

The dominant interference activity of <protein>Ikaros isoforms</protein> unable to bind DNA and their effects in lymphocyte development suggest that <protein>Ikaros</protein> works in concert with other factors .


The role of Aiolos , a lymphoid-restricted and structurally related gene , in lymphoid differentiation is discussed .

The role of <dna>Aiolos</dna> , a <dna>lymphoid-restricted and structurally related gene</dna> , in lymphoid differentiation is discussed .


A model is proposed that defines Ikaros as the backbone of a complex regulatory protein network that controls cell fate decisions and regulates homeostasis in the hemo-lymphoid system .

A model is proposed that defines <protein>Ikaros</protein> as the backbone of a <protein>complex regulatory protein network</protein> that controls cell fate decisions and regulates homeostasis in the hemo-lymphoid system .


Changes in this regulatory network may reflect differentiation and proliferation adjustments made in hemo-lymphoid progenitors and precursors as they give rise to the cells of our immune system .

Changes in this regulatory network may reflect differentiation and proliferation adjustments made in <cell_type>hemo-lymphoid progenitors</cell_type> and <cell_type>precursors</cell_type> as they give rise to the cells of our immune system .


STAT1 pathway is involved in activation of caprine arthritis-encephalitis virus long terminal repeat in monocytes .

<protein>STAT1</protein> pathway is involved in activation of caprine <dna>arthritis-encephalitis virus long terminal repeat</dna> in <cell_type>monocytes</cell_type> .


The caprine arthritis-encephalitis virus ( CAEV ) long terminal repeat ( LTR ) is activated by gamma interferon ( IFN-gamma ) in promonocytic cells .

The <dna>caprine arthritis-encephalitis virus ( CAEV ) long terminal repeat</dna> ( <dna>LTR</dna> ) is activated by <protein>gamma interferon</protein> ( <protein>IFN-gamma</protein> ) in <cell_type>promonocytic cells</cell_type> .


We have previously shown that a 70-bp element is necessary and sufficient for the response of the CAEV LTR to this cytokine .

We have previously shown that a <dna>70-bp element</dna> is necessary and sufficient for the response of the <dna>CAEV LTR</dna> to this <protein>cytokine</protein> .


At the 5 ' end , this 70-bp IFN-gamma response element contains sequence similarity to the gamma activated site ( GAS ) .

At the <dna>5 ' end</dna> , this <dna>70-bp IFN-gamma response element</dna> contains sequence similarity to the <dna>gamma activated site</dna> ( <dna>GAS</dna> ) .


Here we demonstrate that the putative GAS element in the CAEV LTR binds specifically to a cellular factor induced by IFN-gamma in promonocytic cells .

Here we demonstrate that the putative <dna>GAS element</dna> in the <dna>CAEV LTR</dna> binds specifically to a <protein>cellular factor</protein> induced by <protein>IFN-gamma</protein> in <cell_type>promonocytic cells</cell_type> .


Substitution mutations in this consensus sequence eliminate binding of the inducible factor .

Substitution mutations in this <dna>consensus sequence</dna> eliminate binding of the <protein>inducible factor</protein> .


The GAS element from the 70-bp motif is sufficient to confer responsiveness to IFN-gamma using a heterologous minimal promoter .

The <dna>GAS element</dna> from the <dna>70-bp motif</dna> is sufficient to confer responsiveness to <protein>IFN-gamma</protein> using a heterologous minimal promoter .


Consistent with the binding data , the same mutations in the GAS element eliminate responsiveness to IFN-gamma in the context of both a functional CAEV LTR and a heterologous promoter .

Consistent with the binding data , the same mutations in the <dna>GAS element</dna> eliminate responsiveness to <protein>IFN-gamma</protein> in the context of both a functional <dna>CAEV LTR</dna> and a <dna>heterologous promoter</dna> .


The cellular factor that binds to the GAS element is present from 5 min to 14 h after stimulation with IFN-gamma .

The cellular factor that binds to the <dna>GAS element</dna> is present from 5 min to 14 h after stimulation with <protein>IFN-gamma</protein> .


Binding of the nuclear factor to the GAS element in the CAEV LTR is inhibited by antibody directed against STAT1 ( p91/84 ) .

Binding of the nuclear factor to the <dna>GAS element</dna> in the <dna>CAEV LTR</dna> is inhibited by antibody directed against <protein>STAT1</protein> ( <protein>p91/84</protein> ) .


Thus , the GAS sequence in the CAEV LTR is essential for the response to IFN-gamma and a STAT1-like factor binds to this site .

Thus , the GAS sequence in the <dna>CAEV LTR</dna> is essential for the response to <protein>IFN-gamma</protein> and a <protein>STAT1-like factor</protein> binds to this site .


The STAT-1 signaling pathway provides at least one mechanism for activation of the CAEV LTR by IFN-gamma in monocytes .

The STAT-1 signaling pathway provides at least one mechanism for activation of the <dna>CAEV LTR</dna> by <protein>IFN-gamma</protein> in <cell_type>monocytes</cell_type> .


These data are the first demonstration of a role for a STAT family member in the regulation of a viral promoter .

These data are the first demonstration of a role for a <protein>STAT family member</protein> in the regulation of a <dna>viral promoter</dna> .


1 , 25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with renal insufficiency .

<dna>1 , 25-Dihydroxyvitamin D3 receptors</dna> in <cell_type>peripheral blood mononuclear cells</cell_type> from patients with renal insufficiency .


A reduced expression of the vitamin D receptor ( VDR ) in parathyroid glands of uremic animals and humans has been observed .

A reduced expression of the <protein>vitamin D receptor</protein> ( VDR ) in parathyroid glands of uremic animals and humans has been observed .


Similar results have been obtained by our own group in peripheral blood mononuclear cells ( PBMC ) from patients with secondary hyperparathyroidism to chronic renal failure .

Similar results have been obtained by our own group in <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) from patients with secondary hyperparathyroidism to chronic renal failure .


However , the reasons for these changes are not clear .


In the present study , we have investigated the specific uptake of [ 3H ] 1 , 25 ( OH ) 2D3 by PBMC of 11 women with advanced chronic renal failure ( A-CRF ) , 6 women with mild-moderate renal insufficiency ( M-CRF ) , and 23 healthy women .

In the present study , we have investigated the specific uptake of [ 3H ] 1 , 25 ( OH ) 2D3 by <cell_type>PBMC</cell_type> of 11 women with advanced chronic renal failure ( A-CRF ) , 6 women with mild-moderate renal insufficiency ( M-CRF ) , and 23 healthy women .


The mean dissociation constant ( KD ) was similar in both groups of patients and in healthy women ( A-CRF : 0.7 +/- 0.5 x 10 ( -10 ) M ; M-CRF : 1.1 +/- 0.9 x 10 ( -10 ) M ; controls : 1.0 +/- 0.6 x 10 ( -10 ) M ) .


However , VDR concentration was significantly decreased in A-CRF ( 0.8 +/- 0.5 fmol/10 ( 7 ) cells vs. 2.3 +/- 0.9 fmol/10 ( 7 ) cells in controls , p < 0.001 ) , whereas no changes were seen in M-CRF ( 1.7 +/- 0.7 fmol/10 ( 7 ) cells vs. 2.3 +/- 0.9 fmol/10 ( 7 ) cells in controls ) .

However , <protein>VDR</protein> concentration was significantly decreased in A-CRF ( 0.8 +/- 0.5 fmol/10 ( 7 ) cells vs. 2.3 +/- 0.9 fmol/10 ( 7 ) cells in controls , p < 0.001 ) , whereas no changes were seen in M-CRF ( 1.7 +/- 0.7 fmol/10 ( 7 ) cells vs. 2.3 +/- 0.9 fmol/10 ( 7 ) cells in controls ) .


No correlation was seen between VDR and serum calcitriol or PTH levels , when considering both groups of patients together or separately .

No correlation was seen between <protein>VDR</protein> and serum calcitriol or PTH levels , when considering both groups of patients together or separately .


Conversely , a significant negative correlation was found between VDR and serum creatinine values when A-CRF and M-CRF were considered altogether ( r = -0.63 ; p < 0.01 ) .

Conversely , a significant negative correlation was found between <protein>VDR</protein> and serum creatinine values when A-CRF and M-CRF were considered altogether ( r = -0.63 ; p < 0.01 ) .


Treatment with two different schedules of oral calcitriol ( five patients with 0.5 microgram/day for 1 month and four patients with 2 micrograms/day for 7 days ) did not change VDR concentrations .

Treatment with two different schedules of oral calcitriol ( five patients with 0.5 microgram/day for 1 month and four patients with 2 micrograms/day for 7 days ) did not change <protein>VDR</protein> concentrations .


We conclude that the low levels of serum 1 , 25 ( OH ) 2D3 of uremia are not responsible for the decrease in VDR concentration found in these patients .

We conclude that the low levels of serum 1 , 25 ( OH ) 2D3 of uremia are not responsible for the decrease in <protein>VDR</protein> concentration found in these patients .


Transcription factor binding to the core promoter of the human monoamine oxidase B gene in the cerebral cortex and in blood cells .

<protein>Transcription factor</protein> binding to the <dna>core promoter</dna> of the <dna>human monoamine oxidase B gene</dna> in the cerebral cortex and in <cell_type>blood cells</cell_type> .


Many studies show that monoamine oxidase B in blood cells is a biological marker for personality characteristics such as sensation seeking .

Many studies show that <protein>monoamine oxidase B</protein> in <cell_type>blood cells</cell_type> is a biological marker for personality characteristics such as sensation seeking .


The mechanism underlying this association is so far not explored .


In the present study we have performed electrophoretic mobility-shift assays to investigate the pattern of protein binding to a 150 bp fragment of the proximal 5'-flanking region of the human monoamine oxidase B gene .

In the present study we have performed electrophoretic mobility-shift assays to investigate the pattern of protein binding to a <dna>150 bp fragment</dna> of the <dna>proximal 5'-flanking region</dna> of the <dna>human monoamine oxidase B gene</dna> .


We compared the pattern using nuclear extracts from human brain and lymphocytes .

We compared the pattern using nuclear extracts from human brain and <cell_type>lymphocytes</cell_type> .


Interestingly , a correlation was observed between monoamine oxidase B enzyme activity in blood cells ( platelets ) and the binding pattern of two uncharacterized transcription factors .

Interestingly , a correlation was observed between <protein>monoamine oxidase B</protein> enzyme activity in <cell_type>blood cells</cell_type> ( <cell_type>platelets</cell_type> ) and the binding pattern of two uncharacterized <protein>transcription factors</protein> .


These data are well in line with the long-standing notion that interindividual differences in platelet monoamine oxidase may represent differences in expression of the enzyme rather than genotypic variation .

These data are well in line with the long-standing notion that interindividual differences in <protein>platelet monoamine oxidase</protein> may represent differences in expression of the enzyme rather than genotypic variation .


Enhanced differentiation of HL-60 leukemia cells to macrophages induced by ciprofibrate .

Enhanced differentiation of <cell_line>HL-60 leukemia cells</cell_line> to <cell_type>macrophages</cell_type> induced by ciprofibrate .


Ciprofibrate , an hypolipidaemic peroxisome proliferator , induced differentiation of HL-60 cells .

Ciprofibrate , an hypolipidaemic peroxisome proliferator , induced differentiation of <cell_line>HL-60 cells</cell_line> .


The effect was greatly potentiated by phorbol 12-myristate 13-acetate at a concentration where neither phorbol ester nor ciprofibrate alone had any effect on these cells .


As occurs for HL-60 cell differentiation induced by high phorbol ester concentration , the ciprofibrate-induced phorbol ester-dependent differentiation of HL-60 cells proceeded through the monocytic/macrophage pathway and induced the phosphorylation of proteins with similar molecular weights suggesting that increased protein kinase C activity may be involved in the effect .

As occurs for HL-60 cell differentiation induced by high phorbol ester concentration , the ciprofibrate-induced phorbol ester-dependent differentiation of <cell_line>HL-60 cells</cell_line> proceeded through the monocytic/macrophage pathway and induced the phosphorylation of proteins with similar molecular weights suggesting that increased <protein>protein kinase C</protein> activity may be involved in the effect .


The peroxisome proliferator-activated receptor ( PPARalpha ) transcription factor is expressed in HL-60 cells , but no changes were observed in its expression upon HL-60 cell differentiation .

The peroxisome proliferator-activated receptor ( PPARalpha ) <protein>transcription factor</protein> is expressed in <cell_line>HL-60 cells</cell_line> , but no changes were observed in its expression upon HL-60 cell differentiation .


The involvement of multiple tumor necrosis factor receptor ( TNFR ) -associated factors in the signaling mechanisms of receptor activator of NF-kappaB , a member of the TNFR superfamily .

The involvement of multiple <protein>tumor necrosis factor receptor ( TNFR ) -associated factors</protein> in the signaling mechanisms of <protein>receptor activator</protein> of <protein>NF-kappaB</protein> , a member of the <protein>TNFR superfamily</protein> .


Receptor activator of NF-kappaB ( RANK ) is a recently identified member of the tumor necrosis factor receptor superfamily and is expressed on activated T cells and dendritic cells .

<protein>Receptor activator of NF-kappaB</protein> ( <protein>RANK</protein> ) is a recently identified member of the <protein>tumor necrosis factor receptor superfamily</protein> and is expressed on <cell_type>activated T cells</cell_type> and <cell_type>dendritic cells</cell_type> .


Its cognate ligand ( RANKL ) plays significant roles in the activation of dendritic cell function and osteoclast differentiation .

Its <protein>cognate ligand</protein> ( <protein>RANKL</protein> ) plays significant roles in the activation of dendritic cell function and osteoclast differentiation .


We demonstrate here the interaction of RANK with tumor necrosis factor receptor-associated factors ( TRAFs ) 1 , 2 , 3 , 5 , and 6 both in vitro and in cells .

We demonstrate here the interaction of <protein>RANK</protein> with <protein>tumor necrosis factor receptor-associated factors ( TRAFs ) 1 , 2 , 3 , 5 , and 6</protein> both in vitro and in cells .


Mapping of the structural requirements for TRAF /RANK interaction revealed multiple TRAF binding sites clustered in two distinct domains in the RANK cytoplasmic tail .

Mapping of the structural requirements for <protein>TRAF</protein> <protein>/RANK</protein> interaction revealed multiple <protein>TRAF binding sites</protein> clustered in two distinct domains in the <protein>RANK cytoplasmic tail</protein> .


These TRAF binding domains were shown to be functionally important for the RANK -dependent induction of NF-kappaB and c-Jun NH2-terminal kinase activities .

These <protein>TRAF binding domains</protein> were shown to be functionally important for the <protein>RANK</protein> -dependent induction of <protein>NF-kappaB</protein> and <protein>c-Jun</protein> <protein>NH2-terminal kinase</protein> activities .


Site-directed mutagenesis demonstrated that these TRAF binding sites exhibited selective binding for different TRAF proteins .

Site-directed mutagenesis demonstrated that these <protein>TRAF binding sites</protein> exhibited selective binding for different <protein>TRAF proteins</protein> .


In particular , TRAF6 interacted with membrane-proximal determinants distinct from those binding TRAFs 1 , 2 , 3 , and 5 .

In particular , <protein>TRAF6</protein> interacted with <protein>membrane-proximal determinants</protein> distinct from those binding <protein>TRAFs 1 , 2 , 3 , and 5</protein> .


When this membrane-proximal TRAF6 interaction domain was deleted , RANK -mediated NF-kappaB signaling was completely inhibited while c-Jun NH2-terminal kinase activation was partially inhibited .

When this <protein>membrane-proximal TRAF6 interaction domain</protein> was deleted , <protein>RANK</protein> -mediated <protein>NF-kappaB</protein> signaling was completely inhibited while <protein>c-Jun NH2-terminal kinase</protein> activation was partially inhibited .


An NH2-terminal truncation mutant of TRAF6 inhibited RANKL -mediated NF-kappaB activation , but failed to affect constitutive signaling induced by receptor overexpression , revealing a selective role for TRAF6 in ligand-induced activation events .

An <protein>NH2-terminal truncation mutant</protein> of <protein>TRAF6</protein> inhibited <protein>RANKL</protein> -mediated <protein>NF-kappaB</protein> activation , but failed to affect constitutive signaling induced by receptor overexpression , revealing a selective role for <protein>TRAF6</protein> in ligand-induced activation events .


Stat6 inhibits human interleukin-4 promoter activity in T cells .

<protein>Stat6</protein> inhibits human <dna>interleukin-4 promoter</dna> activity in <cell_type>T cells</cell_type> .


The differentiation of naive T-helper ( Th ) cells into cytokine-secreting effector Th cells requires exposure to multiple signals , including exogenous cytokines .

The differentiation of <cell_type>naive T-helper ( Th ) cells</cell_type> into <cell_type>cytokine-secreting effector Th cells</cell_type> requires exposure to multiple signals , including <protein>exogenous cytokines</protein> .


Interleukin-4 ( IL-4 ) plays a major role in this process by promoting the differentiation of IL-4 -secreting Th2 cells .

<protein>Interleukin-4</protein> ( <protein>IL-4</protein> ) plays a major role in this process by promoting the differentiation of <protein>IL-4</protein> -secreting Th2 cells .


In Th2 cells , IL-4 gene expression is tightly controlled at the level of transcription by the coordinated binding of multiple transcription factors to regulatory elements in the proximal promoter region .

In Th2 cells , <protein>IL-4</protein> gene expression is tightly controlled at the level of transcription by the coordinated binding of multiple <protein>transcription factors</protein> to regulatory elements in the proximal <dna>promoter region</dna> .


Nuclear factor of activated T cell ( NFAT ) family members play a critical role in regulating IL-4 transcription and interact with up to five sequences ( termed P0 through P4 ) in the IL-4 promoter .

<protein>Nuclear factor of activated T cell ( NFAT ) family members</protein> play a critical role in regulating <protein>IL-4</protein> transcription and interact with up to five sequences ( termed P0 through P4 ) in the <dna>IL-4 promoter</dna> .


The molecular mechanisms by which IL-4 induces expression of the IL-4 gene are not known , although the IL-4-activated transcription factor signal transducer and activator of transcription 6 ( Stat6 ) is required for this effect .

The molecular mechanisms by which <protein>IL-4</protein> induces expression of the <dna>IL-4 gene</dna> are not known , although the <protein>IL-4-activated transcription factor signal transducer and activator of transcription 6</protein> ( <protein>Stat6</protein> ) is required for this effect .


We report here that Stat6 interacts with three binding sites in the human IL-4 promoter by electrophoretic mobility shift assays .

We report here that <protein>Stat6</protein> interacts with three binding sites in the <dna>human IL-4 promoter</dna> by electrophoretic mobility shift assays .


These sites overlap the P1 , P2 , and P4 NFAT elements .

These sites overlap the <dna>P1 , P2 , and P4 NFAT elements</dna> .


To investigate the role of Stat6 in regulating IL-4 transcription , we used Stat6 -deficient Jurkat T cells with different intact IL-4 promoter constructs in cotransfection assays .

To investigate the role of <protein>Stat6</protein> in regulating <protein>IL-4</protein> transcription , we used <protein>Stat6</protein> -deficient Jurkat <cell_type>T cells</cell_type> with different intact <dna>IL-4 promoter constructs</dna> in cotransfection assays .


We show that , whereas a multimerized response element from the germline IgE promoter was highly induced by IL-4 in Stat6-expressing Jurkat cells , the intact human IL-4 promoter was repressed under similar conditions .

We show that , whereas a <dna>multimerized response element</dna> from the <dna>germline IgE promoter</dna> was highly induced by <protein>IL-4</protein> in <cell_type>Stat6-expressing Jurkat cells</cell_type> , the intact <dna>human IL-4 promoter</dna> was repressed under similar conditions .


We conclude that the function of Stat6 is highly dependent on promoter context and that this factor promotes IL-4 gene expression in an indirect manner .

We conclude that the function of <protein>Stat6</protein> is highly dependent on promoter context and that this factor promotes <protein>IL-4</protein> gene expression in an indirect manner .


Epithelial cell-initiated inflammation plays a crucial role in early tissue damage in amebic infection of human intestine .


BACKGROUND & AIMS : Entamoeba histolytica infection of the intestine can induce severe gut inflammation .


The aims of this study were to assess the role of the host inflammatory response in the tissue damage observed with amebiasis and the role of the intestinal epithelial cell in initiating that response .

The aims of this study were to assess the role of the host inflammatory response in the tissue damage observed with amebiasis and the role of the <cell_type>intestinal epithelial cell</cell_type> in initiating that response .


METHODS : E. histolytica infection was established in human intestinal xenografts in severe combined immunodeficient ( SCID-HU-INT ) mice .


Human intestinal epithelial cell inflammatory responses to amebic infection were inhibited by the intraluminal administration of an antisense oligonucleotide to the human p65 subunit of nuclear factor kappaB , and the role of neutrophils in tissue damage observed with amebiasis was studied by depleting neutrophils from SCID-HU-INT mice .

Human <cell_type>intestinal epithelial cell</cell_type> inflammatory responses to amebic infection were inhibited by the intraluminal administration of an antisense oligonucleotide to the <protein>human p65 subunit</protein> of <protein>nuclear factor kappaB</protein> , and the role of neutrophils in tissue damage observed with amebiasis was studied by depleting <cell_type>neutrophils</cell_type> from SCID-HU-INT mice .


RESULTS : Administration of the antisense oligonucleotide blocked the production of human interleukin 1beta and interleukin 8 by intestinal epithelial cells and inhibited neutrophil influx into the E. histolytica-infected intestinal xenografts .

RESULTS : Administration of the antisense oligonucleotide blocked the production of <protein>human interleukin 1beta</protein> and <protein>interleukin 8</protein> by <cell_type>intestinal epithelial cells</cell_type> and inhibited neutrophil influx into the E. histolytica-infected intestinal xenografts .


Inhibition of the gut inflammatory response by the antisense oligonucleotide or the depletion of neutrophils from SCID-HU- INT mice blocked the increase in intestinal permeability observed with amebic infection .

Inhibition of the gut inflammatory response by the antisense oligonucleotide or the depletion of <cell_type>neutrophils</cell_type> from SCID-HU- INT mice blocked the increase in intestinal permeability observed with amebic infection .


CONCLUSIONS : Intestinal epithelial cells initiate an inflammatory response with resulting neutrophil-mediated tissue damage in response to E. histolytica infection ; this inflammatory cascade can be blocked by inhibiting the transcription of genes regulated by nuclear factor kappaB .

CONCLUSIONS : <cell_type>Intestinal epithelial cells</cell_type> initiate an inflammatory response with resulting neutrophil-mediated tissue damage in response to E. histolytica infection ; this inflammatory cascade can be blocked by inhibiting the transcription of genes regulated by <protein>nuclear factor kappaB</protein> .


Triptolide induces apoptotic death of T lymphocyte .

Triptolide induces apoptotic death of <cell_type>T lymphocyte</cell_type> .


Extract of Tripterygium wilfordii Hook. f ( TWHf ) has immunosuppressive activity and has been used as anti-inflammatory agent in traditional Chinese medicine for centuries .


Recent studies have demonstrated that triptolide is the major active component in the extract that inhibits antigen or mitogen -induced T cell proliferation .

Recent studies have demonstrated that triptolide is the major active component in the extract that inhibits antigen or <protein>mitogen</protein> -induced T cell proliferation .


In attempting to investigate its effect on activation of T lymphocytes , we found triptolide induces apoptotic death of T cell hybridomas and peripheral T cells but not that of thymocytes .

In attempting to investigate its effect on activation of <cell_type>T lymphocytes</cell_type> , we found triptolide induces apoptotic death of <cell_line>T cell hybridomas</cell_line> and <cell_type>peripheral T cells</cell_type> but not that of <cell_type>thymocytes</cell_type> .


The triptolide-induced apoptosis is accompanied by increase of DEVD-cleavable caspases activity and degradation of caspase substrate poly ( ADP-ribose ) polymerase ( PARP ) .

The triptolide-induced apoptosis is accompanied by increase of DEVD-cleavable <protein>caspases</protein> activity and degradation of <protein>caspase substrate poly ( ADP-ribose ) polymerase</protein> ( <protein>PARP</protein> ) .


A specific inhibitor of caspases , zVAD-FMK , prevents triptolide-induced PARP degradation and DNA fragmentation but not growth arrest .

A specific inhibitor of <protein>caspases</protein> , zVAD-FMK , prevents triptolide-induced <protein>PARP</protein> degradation and DNA fragmentation but not growth arrest .


Furthermore , enforced expression of Bcl-2 inhibited triptolide-induced degradation of PARP and apoptosis .

Furthermore , enforced expression of <protein>Bcl-2</protein> inhibited triptolide-induced degradation of <protein>PARP</protein> and apoptosis .


These results indicate that triptolide induces T cell apoptosis through activating caspases , and suggest the growth arrest and apoptotic effect of triptolide may contribute to the immunosuppressive activity of TWHf extract

These results indicate that triptolide induces T cell apoptosis through activating <protein>caspases</protein> , and suggest the growth arrest and apoptotic effect of triptolide may contribute to the immunosuppressive activity of TWHf extract


A novel transcription factor regulates expression of the vacuolar H+-ATPase B2 subunit through AP-2 sites during monocytic differentiation .

A novel <protein>transcription factor</protein> regulates expression of the <protein>vacuolar H+-ATPase B2 subunit</protein> through <dna>AP-2 sites</dna> during monocytic differentiation .


During monocyte-to-macrophage differentiation , the cellular content of vacuolar H+-ATPase ( V-ATPase ) increases more than 4-fold .

During monocyte-to-macrophage differentiation , the cellular content of <protein>vacuolar H+-ATPase</protein> ( <protein>V-ATPase</protein> ) increases more than 4-fold .


We have shown previously that amplified expression of the B2 subunit of the V-ATPase occurs solely by increased transcription , and that the 5'-untranslated region of the B2 gene , containing multiple consensus binding sites for the transcription factors AP-2 and Sp1 , is required for this expression .

We have shown previously that amplified expression of the <protein>B2 subunit</protein> of the <protein>V-ATPase</protein> occurs solely by increased transcription , and that the <dna>5'-untranslated region</dna> of the <dna>B2 gene</dna> , containing multiple <dna>consensus binding sites</dna> for the <protein>transcription factors</protein> <protein>AP-2</protein> and <protein>Sp1</protein> , is required for this expression .


The present study demonstrates that AP-2 binding sequences are essential for increased transcription from the B2 promoter during monocyte-macrophage differentiation and that AP-2 , expressed exogenously in THP-1 and other cells , activates transcription from the B2 promoter .

The present study demonstrates that <dna>AP-2 binding sequences</dna> are essential for increased transcription from the <dna>B2 promoter</dna> during monocyte-macrophage differentiation and that <protein>AP-2</protein> , expressed exogenously in <cell_line>THP-1</cell_line> and other cells , activates transcription from the <dna>B2 promoter</dna> .


In mobility shift assays , a nuclear factor from THP-1 and U-937 cells was identified that binds to several AP-2 response elements within the B2 promoter , but does not react with AP-2 antibodies , and has a DNA sequence binding affinity profile that differs from AP-2 .

In mobility shift assays , a <protein>nuclear factor</protein> from <cell_line>THP-1</cell_line> and <cell_line>U-937 cells</cell_line> was identified that binds to several <dna>AP-2 response elements</dna> within the <dna>B2 promoter</dna> , but does not react with <protein>AP-2 antibodies</protein> , and has a <dna>DNA sequence</dna> binding affinity profile that differs from <protein>AP-2</protein> .


These findings suggest that a novel AP-2-like transcription factor is responsible for V-ATPase B subunit amplification during monocyte differentiation .

These findings suggest that a novel <protein>AP-2-like transcription factor</protein> is responsible for <protein>V-ATPase B subunit</protein> amplification during monocyte differentiation .


c-Jun and GST-pi expression in human plasma cells .

c-Jun and GST-pi expression in <cell_type>human plasma cells</cell_type> .


Bone marrow samples from 33 patients affected by MM and MGUS , and 8 patients not affected by lymphoproliferative diseases were studied for expression of c-Jun ( a component of the transcription factor AP-1 ) and glutathione-S-transferase pi ( GST-pi ) using immunocytochemical methods .

Bone marrow samples from 33 patients affected by MM and MGUS , and 8 patients not affected by lymphoproliferative diseases were studied for expression of <protein>c-Jun</protein> ( a component of the <protein>transcription factor</protein> <protein>AP-1</protein> ) and <protein>glutathione-S-transferase pi</protein> ( <protein>GST-pi</protein> ) using immunocytochemical methods .


A high and frequent expression of these two proteins was found both in MM and MGUS patients ( 31/33 patients positive for c-Jun and 29/33 patients positive for GST-pi ) and in controls not affected by monoclonal gammopathy ( 7/8 patients positive for both c-Jun and GST-pi ) .

A high and frequent expression of these two proteins was found both in MM and MGUS patients ( 31/33 patients positive for <protein>c-Jun</protein> and 29/33 patients positive for <protein>GST-pi</protein> ) and in controls not affected by monoclonal gammopathy ( 7/8 patients positive for both <protein>c-Jun</protein> and <protein>GST-pi</protein> ) .


No statistically significant correlation was found between c-Jun- and GST-pi-positive plasma cells .

No statistically significant correlation was found between <cell_line>c-Jun- and GST-pi-positive plasma cells</cell_line> .


The expression of these two proteins was not related to clinical or laboratory data .


Our results seem to confirm a possible role of the transcriptional complex AP-1 in activating GST-pi promoter in human plasma cells .

Our results seem to confirm a possible role of the <protein>transcriptional complex</protein> <protein>AP-1</protein> in activating <dna>GST-pi promoter</dna> in <cell_type>human plasma cells</cell_type> .


Activation of signaling pathways and prevention of apoptosis by cytokines in eosinophils .

Activation of signaling pathways and prevention of apoptosis by <protein>cytokines</protein> in <cell_type>eosinophils</cell_type> .


Inhibition of apoptosis in eosinophils by cytokines such as IL-5 and GM-CSF may play an important role in the pathogenesis of allergic and parasitic disorders .

Inhibition of apoptosis in <cell_type>eosinophils</cell_type> by <protein>cytokines</protein> such as <protein>IL-5</protein> and <protein>GM-CSF</protein> may play an important role in the pathogenesis of allergic and parasitic disorders .


Recently , there has been some progress in the understanding of the signal transduction pathways activated by these cytokines in eosinophils .

Recently , there has been some progress in the understanding of the signal transduction pathways activated by these <protein>cytokines</protein> in <cell_type>eosinophils</cell_type> .


The IL-3 , IL-5 and GM-CSF receptors share a common signal transducer that possesses no intrinsic kinase domain .

The <protein>IL-3</protein> , <protein>IL-5</protein> and <protein>GM-CSF receptors</protein> share a <protein>common signal transducer</protein> that possesses no <protein>intrinsic kinase domain</protein> .


It has been shown that eosinophil stimulation by these cytokines is associated with increases in tyrosine phosphorylation of several cellular substrates .

It has been shown that eosinophil stimulation by these <protein>cytokines</protein> is associated with increases in tyrosine phosphorylation of several cellular substrates .


In the past few years , there has been some progress in defining the tyrosine kinases that are activated by the IL-3/IL-5/GM-CSF receptor beta-subunit in eosinophils .

In the past few years , there has been some progress in defining the tyrosine kinases that are activated by the <protein>IL-3/IL-5/GM-CSF receptor beta-subunit</protein> in <cell_type>eosinophils</cell_type> .


This review will concentrate on this topic and on its role for the regulation of eosinophil apoptosis .


Requirement of GATA-1 and p45 NF-E2 expression in butyric acid-induced erythroid differentiation .

Requirement of <protein>GATA-1</protein> and <protein>p45 NF-E2</protein> expression in butyric acid-induced erythroid differentiation .


Butyric acid ( BA ) is known to induce overexpression of fetal hemoglobin and then erythroid differentiation .

Butyric acid ( BA ) is known to induce overexpression of <protein>fetal hemoglobin</protein> and then erythroid differentiation .


Therefore , BA is currently under clinical investigation as a potential therapy for the treatment of sickle cell disease and cancer .


Nevertheless , the molecular mechanisms involved in BA-induced differentiation remain largely unknown .


Previous reports have shown that BA-induced overexpression of erythroid genes occurred at the transcriptional level , suggesting the involvement of erythroid transcription factors .

Previous reports have shown that BA-induced overexpression of <dna>erythroid genes</dna> occurred at the transcriptional level , suggesting the involvement of <protein>erythroid transcription factors</protein> .


Here , we intend to demonstrate the requirement of GATA-1 and NF-E2 transcription factors in the BA-induced erythroid differentiation of human leukemic K562 cells .

Here , we intend to demonstrate the requirement of <protein>GATA-1</protein> and <protein>NF-E2</protein> <protein>transcription factors</protein> in the BA-induced erythroid differentiation of <cell_line>human leukemic K562 cells</cell_line> .


Time-course experiments showed that nuclear levels of GATA-1 and p45 NF-E2 proteins increased during BA treatment .

Time-course experiments showed that nuclear levels of <protein>GATA-1</protein> and <protein>p45 NF-E2</protein> proteins increased during BA treatment .


Moreover , antisense oligodeoxynucleotides targeting either GATA-1 or p45 NF-E2 proteins inhibited both protein expression and BA-induced differentiation .

Moreover , antisense oligodeoxynucleotides targeting either <protein>GATA-1</protein> or <protein>p45 NF-E2</protein> proteins inhibited both protein expression and BA-induced differentiation .


In contrast , BA-induced cell growth inhibition was not affected .


These results provide the first direct evidence for the requirement of GATA-1 and NF-E2 in BA-induced differentiation process .

These results provide the first direct evidence for the requirement of <protein>GATA-1</protein> and <protein>NF-E2</protein> in BA-induced differentiation process .


Characterisation of regulatory sequences at the Epstein-Barr virus BamHI W promoter .

Characterisation of regulatory sequences at the <dna>Epstein-Barr virus BamHI W promoter</dna> .


Epstein-Barr virus , a human gammaherpesvirus , possesses a unique set of latent genes whose constitutive expression in B cells leads to cell growth transformation .

Epstein-Barr virus , a human gammaherpesvirus , possesses a unique set of <dna>latent genes</dna> whose constitutive expression in <cell_type>B cells</cell_type> leads to cell growth transformation .


The initiation of this growth transforming infection depends on a viral promoter in BamHI W ( Wp ) whose regulation is poorly understood .

The initiation of this growth transforming infection depends on a <dna>viral promoter</dna> in BamHI W ( Wp ) whose regulation is poorly understood .


Using Wp reporter constructs in in vitro transfection assays , we found that Wp was 11- to 190-fold more active in B cell than in non-B cell lines and that three regions of the promoter ( termed UAS1 , UAS2 , and UAS3 ) contributed to transcriptional activation .

Using <dna>Wp reporter constructs</dna> in in vitro transfection assays , we found that Wp was 11- to 190-fold more active in <cell_line>B cell</cell_line> than in <cell_line>non-B cell lines</cell_line> and that three regions of the <dna>promoter</dna> ( termed <dna>UAS1</dna> , <dna>UAS2</dna> , and <dna>UAS3</dna> ) contributed to transcriptional activation .


The upstream regions UAS3 ( -1168 to -440 ) and UAS2 ( -352 to -264 ) both functioned in a cell lineage-independent manner and were together responsible for the bulk of Wp activity in non-B cells ; mutational analysis indicated the importance of a YY1 binding site in UAS2 in that context .

The upstream regions <dna>UAS3</dna> ( <dna>-1168 to -440</dna> ) and <dna>UAS2</dna> ( <dna>-352 to -264</dna> ) both functioned in a cell lineage-independent manner and were together responsible for the bulk of Wp activity in <cell_type>non-B cells</cell_type> ; mutational analysis indicated the importance of a <dna>YY1 binding site</dna> in <dna>UAS2</dna> in that context .


By contrast , UAS1 ( -140 to -87 ) was B cell specific and was the key determinant of the promoter 's increased activity in B cell lines .

By contrast , <dna>UAS1</dna> ( <dna>-140 to -87</dna> ) was B cell specific and was the key determinant of the promoter 's increased activity in <cell_line>B cell lines</cell_line> .


Mutational analysis of UAS1 sequences combined with in vitro bandshift assays revealed the presence of three binding sites for cellular factors in this region .

Mutational analysis of <dna>UAS1 sequences</dna> combined with in vitro bandshift assays revealed the presence of three <dna>binding sites</dna> for <protein>cellular factors</protein> in this region .


When mutations that abolished factor binding in bandshift assays were introduced into a Wp reporter construct , the loss of any one of the three UAS1 binding sites was sufficient to reduce promoter activity by 10- to 30-fold in B cells .

When mutations that abolished factor binding in bandshift assays were introduced into a <dna>Wp reporter construct</dna> , the loss of any one of the three <dna>UAS1 binding sites</dna> was sufficient to reduce promoter activity by 10- to 30-fold in <cell_type>B cells</cell_type> .


From sequence analysis , two of these appear to be novel transcription factor binding sites , whereas the third was identified as a cyclic AMP response element ( CRE ) .

From sequence analysis , two of these appear to be novel <protein>transcription factor</protein> <dna>binding sites</dna> , whereas the third was identified as a <dna>cyclic AMP response element</dna> ( <dna>CRE</dna> ) .


Our data indicate that this CRE interacts with CREB and ATF1 proteins present in B cell nuclear extracts and that this interaction is important for Wp activity .

Our data indicate that this <dna>CRE</dna> interacts with <protein>CREB and ATF1 proteins</protein> present in B cell nuclear extracts and that this interaction is important for Wp activity .


In situ RT-PCR detection of Epstein-Barr virus immediate-early transcripts in CD4+ and CD8+ T lymphocytes .

In situ RT-PCR detection of <rna>Epstein-Barr virus immediate-early transcripts</rna> in <cell_type>CD4+ and CD8+ T lymphocytes</cell_type> .


AIDS-related Epstein-Barr virus ( EBV ) -associated T cell lymphomas are emerging as a new , distinct histopathological entity .


The pathway whereby EBV infects T cells as well as the initial EBV transcriptional program in T cells has not been established .

The pathway whereby EBV infects <cell_type>T cells</cell_type> as well as the initial EBV transcriptional program in <cell_type>T cells</cell_type> has not been established .


In order to shed light on the early events of the EBV infection of T cells , we have used in situ reverse transcription based polymerase chain reaction ( RT-PCR ) to study the initial EBV transcriptional program in homogeneous CD4+ and CD8+ lymphocytes .

In order to shed light on the early events of the EBV infection of <cell_type>T cells</cell_type> , we have used in situ reverse transcription based polymerase chain reaction ( RT-PCR ) to study the initial EBV transcriptional program in <cell_type>homogeneous CD4+ and CD8+ lymphocytes</cell_type> .


Following EBV infection , Epstein-Barr nuclear antigen ( EBNA ) expression could be detected in T rosetting CD4+ and CD8+ T lymphocytes .

Following EBV infection , Epstein-Barr nuclear antigen ( <protein>EBNA</protein> ) expression could be detected in <cell_type>T rosetting CD4+ and CD8+ T lymphocytes</cell_type> .


Only a few cells showed viral capsid antigen ( VCA ) .

Only a few cells showed <protein>viral capsid antigen</protein> ( <protein>VCA</protein> ) .


EBV immediate-early gene transcripts ( BZLF1 , BRLF1 , and BMLF1 ) encoded in the BamHI Z , R , and M fragments could be detected by in situ RT-PCR in the EBV producer cell line B95.8 .

<rna>EBV immediate-early gene transcripts</rna> ( <rna>BZLF1</rna> , <rna>BRLF1</rna> , and <rna>BMLF1</rna> ) encoded in the BamHI Z , R , and M fragments could be detected by in situ RT-PCR in the EBV producer cell line B95.8 .


Both BZLF1 and BRLF1 immediate-early transcripts , but not BMLF1 transcript , could be detected in individual CD4+ and CD8+ T cells infected with EBV .

Both <rna>BZLF1 and BRLF1 immediate-early transcripts</rna> , but not <rna>BMLF1 transcript</rna> , could be detected in individual <cell_type>CD4+ and CD8+ T cells</cell_type> infected with EBV .


Demonstration of EBV mRNA transcripts encoding immediate-early transcriptional transactivators in EBV-infected T cells provides the first evidence for a possible mechanism whereby EBV could contribute to T cell proliferation and EBV-associated T cell malignancies .

Demonstration of <rna>EBV mRNA transcripts</rna> encoding <protein>immediate-early transcriptional transactivators</protein> in <cell_type>EBV-infected T cells</cell_type> provides the first evidence for a possible mechanism whereby EBV could contribute to T cell proliferation and EBV-associated T cell malignancies .


The linkage between T-cell and dendritic cell development in the mouse thymus .


Thymic dendritic cells ( DC ) mediate negative selection at a relatively late stage of the T-cell developmental pathway .

<cell_type>Thymic dendritic cells</cell_type> ( <cell_type>DC</cell_type> ) mediate negative selection at a relatively late stage of the T-cell developmental pathway .


We present evidence that the development of thymic DC and of T-lineage cells is linked via a common precursor at an early stage of thymocyte development .

We present evidence that the development of <cell_type>thymic DC</cell_type> and of <cell_type>T-lineage cells</cell_type> is linked via a common precursor at an early stage of thymocyte development .


T-lineage precursor populations from the adult mouse thymus , prior to T-cell receptor gene rearrangement , display a capacity to produce DC as well as T cells in the thymus , and are very efficient precursors of DC in culture .

T-lineage precursor populations from the adult mouse thymus , prior to T-cell receptor gene rearrangement , display a capacity to produce <cell_type>DC</cell_type> as well as <cell_type>T cells</cell_type> in the thymus , and are very efficient precursors of <cell_type>DC</cell_type> in culture .


These lymphoid/DC precursors have little capacity to form myeloid cells , indicating that thymic DC are a lymphoid-related rather than myeloid-related lineage .

These <cell_type>lymphoid/DC precursors</cell_type> have little capacity to form <cell_type>myeloid cells</cell_type> , indicating that <cell_type>thymic DC</cell_type> are a lymphoid-related rather than <cell_type>myeloid-related lineage</cell_type> .


In contrast to myeloid-related DC , granulocyte-macrophage colony-stimulating factor is not required for the development of these lymphoid-related DC in vivo or in vitro .

In contrast to <cell_type>myeloid-related DC</cell_type> , <protein>granulocyte-macrophage colony-stimulating factor</protein> is not required for the development of these <cell_type>lymphoid-related DC</cell_type> in vivo or in vitro .


DC can develop in mutant mice lacking mature T cells , provided the common precursors are present .

<cell_type>DC</cell_type> can develop in mutant mice lacking <cell_type>mature T cells</cell_type> , provided the common precursors are present .


However , in mutant mice lacking functional Ikaros transcription factors , there are deficiencies in lymphoid precursor cells , in mature lymphoid cells and in DC .

However , in mutant mice lacking functional <protein>Ikaros</protein> <protein>transcription factors</protein> , there are deficiencies in <cell_type>lymphoid precursor cells</cell_type> , in <cell_type>mature lymphoid cells</cell_type> and in <cell_type>DC</cell_type> .


Host control of HIV-1 parasitism in T cells by the nuclear factor of activated T cells .

Host control of HIV-1 parasitism in <cell_type>T cells</cell_type> by the <protein>nuclear factor of activated T cells</protein> .


Post HIV-1 entry , productive HIV-1 infection of primary T cells requires overcoming several cellular blocks to provirus establishment and replication .

Post HIV-1 entry , productive HIV-1 infection of <cell_type>primary T cells</cell_type> requires overcoming several cellular blocks to provirus establishment and replication .


Activation of unknown host intracellular events overcomes such inhibitory steps and is concomitant with HIV-1 replication .


We show that the transcription factor NFATc was sufficient as a cellular factor to induce a highly permissive state for HIV-1 replication in primary CD4+ T cells .

We show that the <protein>transcription factor</protein> <protein>NFATc</protein> was sufficient as a cellular factor to induce a highly permissive state for HIV-1 replication in <cell_type>primary CD4+ T cells</cell_type> .


NFATc overcame a blockade at reverse transcription and permitted active HIV-1 replication .

<protein>NFATc</protein> overcame a blockade at reverse transcription and permitted active HIV-1 replication .


Pharmacologic blockade of endogenous NFAT activity by FK506 or CsA inhibited synthesis of reverse transcription and also potently blocked HIV-1 replication .

Pharmacologic blockade of <protein>endogenous NFAT</protein> activity by FK506 or CsA inhibited synthesis of reverse transcription and also potently blocked HIV-1 replication .


T cells therefore can become competent for HIV-1 replication by control of regulated host factors such as the NFATc transcription factor .

<cell_type>T cells</cell_type> therefore can become competent for HIV-1 replication by control of <protein>regulated host factors</protein> such as the <protein>NFATc</protein> <protein>transcription factor</protein> .


The host mechanisms regulated by such permissivity factors are potential targets for anti-HIV-1 therapy .


Regulation of NF-kappa B , AP-1 , NFAT , and STAT1 nuclear import in T lymphocytes by noninvasive delivery of peptide carrying the nuclear localization sequence of NF-kappa B p50 .

Regulation of <protein>NF-kappa B</protein> , <protein>AP-1</protein> , <protein>NFAT</protein> , and <protein>STAT1</protein> nuclear import in <cell_type>T lymphocytes</cell_type> by noninvasive delivery of peptide carrying the <protein>nuclear localization sequence</protein> of <protein>NF-kappa B p50</protein> .


Activation of T lymphocytes by Ags or cytokines results in translocation of the transcription factors NF-kappa B , AP-1 , NFAT , and STAT from the cytoplasm into the nucleus .

Activation of <cell_type>T lymphocytes</cell_type> by <protein>Ags</protein> or <protein>cytokines</protein> results in translocation of the <protein>transcription factors</protein> <protein>NF-kappa B</protein> , <protein>AP-1</protein> , <protein>NFAT</protein> , and <protein>STAT</protein> from the cytoplasm into the nucleus .


The first step in the nuclear import process is recognition of a nuclear localization sequence ( NLS ) within the karyophilic protein by a cytoplasmic receptor such as the importin ( karyopherin ) -alpha subunit .

The first step in the nuclear import process is recognition of a <protein>nuclear localization sequence</protein> ( <protein>NLS</protein> ) within the <protein>karyophilic protein</protein> by a <protein>cytoplasmic receptor</protein> such as the <protein>importin ( karyopherin ) -alpha subunit</protein> .


The NLSs of NF-kappa B , AP-1 , and NFAT differ and the NLS of STAT1 has not yet been identified .

The <protein>NLSs</protein> of <protein>NF-kappa B</protein> , <protein>AP-1</protein> , and <protein>NFAT</protein> differ and the <protein>NLS</protein> of <protein>STAT1</protein> has not yet been identified .


Herein we demonstrate that the inducible nuclear import of NF-kappa B , AP-1 , NFAT , and STAT1 in Jurkat T lymphocytes is significantly inhibited by a cell-permeable peptide carrying the NLS of the NF-kappa B p50 subunit .

Herein we demonstrate that the inducible nuclear import of <protein>NF-kappa B</protein> , <protein>AP-1</protein> , <protein>NFAT</protein> , and <protein>STAT1</protein> in <cell_line>Jurkat T lymphocytes</cell_line> is significantly inhibited by a cell-permeable peptide carrying the <protein>NLS</protein> of the <protein>NF-kappa B p50 subunit</protein> .


NLS peptide-mediated disruption of the nuclear import of these transcription factors results in inhibition of I kappa B alpha and IL-2 gene expression , processes dependent on NF-kappa B or the combination of NF-kappa B , AP-1 , and NFAT .

<protein>NLS</protein> peptide-mediated disruption of the nuclear import of these <protein>transcription factors</protein> results in inhibition of I kappa B alpha and IL-2 gene expression , processes dependent on <protein>NF-kappa B</protein> or the combination of <protein>NF-kappa B</protein> , <protein>AP-1</protein> , and <protein>NFAT</protein> .


Further , we show that inhibitory NLS peptide interacts in vitro with a cytoplasmic NLS receptor complex comprised of the Rch1/importin ( karyopherin ) -beta heterodimer expressed in Jurkat T cells .

Further , we show that inhibitory <protein>NLS</protein> peptide interacts in vitro with a <protein>cytoplasmic NLS receptor complex</protein> comprised of the <protein>Rch1/importin ( karyopherin ) -beta heterodimer</protein> expressed in <cell_line>Jurkat T cells</cell_line> .


Taken together , these data indicate that the inducible nuclear import of NF-kappa B , AP-1 , NFAT , and STAT1 in Jurkat T cells can be regulated by NLS peptide delivered noninvasively to the cytoplasm of Jurkat T cells to target members of the importin ( karyopherin ) -alpha beta NLS receptor complex .

Taken together , these data indicate that the inducible nuclear import of <protein>NF-kappa B</protein> , <protein>AP-1</protein> , <protein>NFAT</protein> , and <protein>STAT1</protein> in <cell_line>Jurkat T cells</cell_line> can be regulated by <protein>NLS</protein> peptide delivered noninvasively to the cytoplasm of <cell_line>Jurkat T cells</cell_line> to target members of the <protein>importin ( karyopherin ) -alpha beta</protein> <protein>NLS receptor complex</protein> .


Membrane-associated lymphotoxin on natural killer cells activates endothelial cells via an NF-kappaB -dependent pathway .

<protein>Membrane-associated lymphotoxin</protein> on <cell_type>natural killer cells</cell_type> activates <cell_type>endothelial cells</cell_type> via an <protein>NF-kappaB</protein> -dependent pathway .


BACKGROUND : Inhibition of complement in small animal models of xenotransplantation has demonstrated graft infiltration with natural killer ( NK ) cells and monocytes associated with endothelial cell ( EC ) activation .

BACKGROUND : Inhibition of complement in small animal models of xenotransplantation has demonstrated graft infiltration with <cell_type>natural killer ( NK ) cells</cell_type> and monocytes associated with <cell_type>endothelial cell</cell_type> ( <cell_type>EC</cell_type> ) activation .


We have previously demonstrated that human NK cells activate porcine EC in vitro , which results in adhesion molecule expression and cytokine secretion .

We have previously demonstrated that <cell_type>human NK cells</cell_type> activate porcine <cell_type>EC</cell_type> in vitro , which results in <protein>adhesion molecule</protein> expression and <protein>cytokine</protein> secretion .


In this study , we used the NK cell line NK92 to define the molecular and cellular basis of NK cell-mediated EC activation .

In this study , we used the <cell_line>NK cell line NK92</cell_line> to define the molecular and cellular basis of NK cell-mediated <cell_type>EC</cell_type> activation .


METHODS : EC were transfected with either reporter constructs containing the luciferase gene driven either by E-selectin or interleukin ( IL ) -8 promoters or a synthetic NF-kappaB-dependent promoter .

METHODS : <cell_type>EC</cell_type> were transfected with either reporter constructs containing the <dna>luciferase gene</dna> driven either by <dna>E-selectin or interleukin ( IL ) -8 promoters</dna> or a synthetic <dna>NF-kappaB-dependent promoter</dna> .


In addition , a dominant-negative mutant tumor necrosis factor receptor I ( TNFRI ) expression vector was co-transfected in inhibition studies .

In addition , a <dna>dominant-negative mutant tumor necrosis factor receptor I ( TNFRI ) expression vector</dna> was co-transfected in inhibition studies .


Forty-eight hours after transfection , EC were stimulated with NK cells or NK cell membrane extracts for 7 hr and activation was measured by a luciferase assay .

Forty-eight hours after transfection , <cell_type>EC</cell_type> were stimulated with <cell_type>NK cells</cell_type> or <cell_type>NK cell membrane extracts</cell_type> for 7 hr and activation was measured by a <protein>luciferase</protein> assay .


RESULTS : Co-culture of NK cells with transfected EC enhanced E-selectin , IL-8 , and NF-kappaB -dependent promoter activity .

RESULTS : Co-culture of <cell_type>NK cells</cell_type> with transfected <cell_type>EC</cell_type> enhanced <protein>E-selectin</protein> , <protein>IL-8</protein> , and <protein>NF-kappaB</protein> -dependent promoter activity .


NK cell membrane extracts retained the capacity to activate EC and induced nuclear translocation of NF-kappaB ( p50 and p65 ) .

NK cell membrane extracts retained the capacity to activate <cell_type>EC</cell_type> and induced nuclear translocation of <protein>NF-kappaB</protein> ( <protein>p50</protein> and <protein>p65</protein> ) .


Western blotting of NK cell and membrane extracts detected the presence of Lymphotoxin-alpha ( LTalpha ) but not tumor necrosis factor-alpha .

Western blotting of <cell_type>NK cell</cell_type> and membrane extracts detected the presence of <protein>Lymphotoxin-alpha</protein> ( <protein>LTalpha</protein> ) but not <protein>tumor necrosis factor-alpha</protein> .


Furthermore , LTalpha was secreted in NK : EC co-cultures .

Furthermore , <protein>LTalpha</protein> was secreted in <cell_line>NK : EC co-cultures</cell_line> .


Co-transfection with dominant-negative mutant TNFRI inhibited EC activation by NK cell membrane extracts and by NK cells by 80 % and 47 % , respectively .

Co-transfection with <protein>dominant-negative mutant TNFRI</protein> inhibited <cell_type>EC</cell_type> activation by NK cell membrane extracts and by <cell_type>NK cells</cell_type> by 80 % and 47 % , respectively .


The same pattern of inhibition was observed using anti-human LT sera .


CONCLUSIONS : Human NK cell membrane-bound LT signals across species via TNFRI , leading to NF-kappaB nuclear translocation and transcription of E-selectin and IL-8 , which results in EC activation .

CONCLUSIONS : Human NK cell membrane-bound LT signals across species via <protein>TNFRI</protein> , leading to <protein>NF-kappaB</protein> nuclear translocation and transcription of <protein>E-selectin</protein> and <protein>IL-8</protein> , which results in <cell_type>EC</cell_type> activation .


The discrepancy in the degree of inhibition by membrane extracts and NK cells with mutant TNFRI suggests that additional pathways are utilized by NK cells to activate EC

The discrepancy in the degree of inhibition by membrane extracts and <cell_type>NK cells</cell_type> with <protein>mutant TNFRI</protein> suggests that additional pathways are utilized by <cell_type>NK cells</cell_type> to activate <cell_type>EC</cell_type>


Ras -dependent , Ca2+-stimulated activation of nuclear factor of activated T cells by a constitutively active Cbl mutant in T cells .

<protein>Ras</protein> -dependent , Ca2+-stimulated activation of <protein>nuclear factor of activated T cells</protein> by a constitutively active <protein>Cbl mutant</protein> in <cell_type>T cells</cell_type> .


T cell receptor ( TCR ) stimulation induces rapid tyrosine phosphorylation of cellular proteins , including Cbl , a protooncogene product whose function remains unclear .

<protein>T cell receptor</protein> ( <protein>TCR</protein> ) stimulation induces rapid tyrosine phosphorylation of <protein>cellular proteins</protein> , including <protein>Cbl</protein> , a <protein>protooncogene product</protein> whose function remains unclear .


As a first step toward elucidating the function of Cbl in TCR -initiated signaling , we evaluated the ability of wild-type Cbl or a transforming Cbl mutant ( 70Z/3 ) to induce transcriptional activation of a nuclear factor of activated T cells ( NFAT ) element derived from the interleukin 2 ( IL2 ) promoter in transiently cotransfected Jurkat-TAg T cells .

As a first step toward elucidating the function of <protein>Cbl</protein> in <protein>TCR</protein> -initiated signaling , we evaluated the ability of <protein>wild-type Cbl</protein> or a transforming <protein>Cbl mutant</protein> ( 70Z/3 ) to induce transcriptional activation of a <dna>nuclear factor of activated T cells ( NFAT ) element</dna> derived from the <dna>interleukin 2 ( IL2 ) promoter</dna> in transiently cotransfected <cell_line>Jurkat-TAg T cells</cell_line> .


70Z/3 , but not Cbl , caused NFAT activation which was significantly enhanced by stimulation with calcium ionophore , and was drastically reduced by cyclosporin A pretreatment .

<protein>70Z/3</protein> , but not <protein>Cbl</protein> , caused <protein>NFAT</protein> activation which was significantly enhanced by stimulation with calcium ionophore , and was drastically reduced by cyclosporin A pretreatment .


A point mutation of a potential phosphatidylinositol 3-kinase ( PI3-K ) binding site ( Y731EAM to Y731EAC ) in 70Z/3 disrupted the association of PI3-K with 70Z/3 , but did not reduce the induction of NFAT activity , suggesting that the interaction between Cbl and PI3-K is not required in the 70Z/3 -mediated induction of NFAT .

A point mutation of a potential <dna>phosphatidylinositol 3-kinase ( PI3-K ) binding site</dna> ( <dna>Y731EAM</dna> to <dna>Y731EAC</dna> ) in <protein>70Z/3</protein> disrupted the association of <protein>PI3-K</protein> with <protein>70Z/3</protein> , but did not reduce the induction of <protein>NFAT</protein> activity , suggesting that the interaction between <protein>Cbl</protein> and <protein>PI3-K</protein> is not required in the <protein>70Z/3</protein> -mediated induction of <protein>NFAT</protein> .


Additional mapping studies indicated that defined deletions of C-terminal 70Z/3 sequences affected to a variable degree its ability to stimulate NFAT activity .

Additional mapping studies indicated that defined deletions of C-terminal <protein>70Z/3</protein> sequences affected to a variable degree its ability to stimulate <protein>NFAT</protein> activity .


Strikingly , deletion of 346 C-terminal residues augmented this activity , whereas removal of 20 additional residues abolished it .

Strikingly , deletion of <protein>346 C-terminal residues</protein> augmented this activity , whereas removal of 20 additional residues abolished it .


Coexpression of dominant negative Ras abrogated the basal or ionomycin-stimulated , 70Z/3 -mediated NFAT activation , suggesting a functional Ras is required for this activation .

Coexpression of <protein>dominant negative Ras</protein> abrogated the basal or ionomycin-stimulated , <protein>70Z/3</protein> -mediated <protein>NFAT</protein> activation , suggesting a <protein>functional Ras</protein> is required for this activation .


These results implicate Cbl in Ras -dependent signaling pathways which lead to NFAT activation .

These results implicate <protein>Cbl</protein> in <protein>Ras</protein> -dependent signaling pathways which lead to <protein>NFAT</protein> activation .


Requirement of prestimulated THP-1 monocytic cells for endothelial cell activation .

Requirement of <cell_line>prestimulated THP-1 monocytic cells</cell_line> for <cell_type>endothelial cell</cell_type> activation .


Involvement of TNF alpha .


Blood monocytes spontaneously activate endothelial cells in culture , leading to adhesion of monocytic cells onto the endothelial surface and overproduction of endothelial proteins such as von Willebrand factor ( vWf ) and plasminogen activator inhibitor type 1 ( PAI-1 ) .

<cell_type>Blood monocytes</cell_type> spontaneously activate <cell_type>endothelial cells</cell_type> in culture , leading to adhesion of <cell_type>monocytic cells</cell_type> onto the endothelial surface and overproduction of endothelial proteins such as <protein>von Willebrand factor</protein> ( <protein>vWf</protein> ) and <protein>plasminogen activator inhibitor type 1</protein> ( <protein>PAI-1</protein> ) .


To overcome the difficulty in obtaining quiescent monocytes , we studied the ability of promonocytic THP-1 cells to activate endothelial cells .

To overcome the difficulty in obtaining <cell_type>quiescent monocytes</cell_type> , we studied the ability of <cell_line>promonocytic THP-1 cells</cell_line> to activate <cell_type>endothelial cells</cell_type> .


Lipopolysaccharide ( LPS ) -prestimulated and untreated THP-1 cells were cocultured with resting human umbilical vein endothelial cells ( HUVEC ) for 3 and 24 h in the presence of colimycin to neutralize LPS traces .

Lipopolysaccharide ( LPS ) -prestimulated and untreated <cell_line>THP-1 cells</cell_line> were cocultured with <cell_type>resting human umbilical vein endothelial cells</cell_type> ( <cell_type>HUVEC</cell_type> ) for 3 and 24 h in the presence of colimycin to neutralize LPS traces .


Addition of untreated THP-1 cells had little effect on HUVEC adhesiveness .

Addition of untreated <cell_line>THP-1 cells</cell_line> had little effect on <cell_type>HUVEC</cell_type> adhesiveness .


Addition of prestimulated THP-1 cells was followed by a noticeable adhesion after 3 h which reversed to basal values within 24 h .

Addition of prestimulated <cell_line>THP-1 cells</cell_line> was followed by a noticeable adhesion after 3 h which reversed to basal values within 24 h .


Under these conditions HUVEC adhesion molecules , E-selectin , VCAM-1 and ICAM-1 , were increased at 3 h with only ICAM-1 remaining overexpressed at 24 h .

Under these conditions <protein>HUVEC adhesion molecules</protein> , <protein>E-selectin</protein> , <protein>VCAM-1</protein> and <protein>ICAM-1</protein> , were increased at 3 h with only <protein>ICAM-1</protein> remaining overexpressed at 24 h .


Diffusible endothelial proteins such as soluble E-selectin , PAI-1 and vWf to a minimal extent , increased in supernatants from HUVEC cocultured for 24 h with prestimulated THP-1 cells .

<protein>Diffusible endothelial proteins</protein> such as soluble <protein>E-selectin</protein> , <protein>PAI-1</protein> and <protein>vWf</protein> to a minimal extent , increased in supernatants from <cell_type>HUVEC</cell_type> cocultured for 24 h with prestimulated <cell_line>THP-1 cells</cell_line> .


In those cocultures , TNF alpha concentrations peaked at 3 h whereas IL-1 beta levels progressively rose until 24 h .

In those cocultures , <protein>TNF alpha</protein> concentrations peaked at 3 h whereas IL-1 beta levels progressively rose until 24 h .


Addition of an anti-TNF alpha antibody decreased by 40 % E-selectin and ICAM-1 induction and suppressed PAI-1 overproduction with a weak effect on vWf .

Addition of an <protein>anti-TNF alpha antibody</protein> decreased by 40 % <protein>E-selectin</protein> and <protein>ICAM-1</protein> induction and suppressed <protein>PAI-1</protein> overproduction with a weak effect on <protein>vWf</protein> .


An anti-IL-1 beta antibody had negligible effects on HUVEC adhesion molecules , PAI-1 or vWf production .

An <protein>anti-IL-1 beta antibody</protein> had negligible effects on <protein>HUVEC adhesion molecules</protein> , <protein>PAI-1</protein> or <protein>vWf</protein> production .


These results provide evidence that promonocytic THP-1 cells require prestimulation in order to activate HUVEC and that TNF alpha contributes to this phenomenon .

These results provide evidence that <cell_line>promonocytic THP-1 cells</cell_line> require prestimulation in order to activate <cell_type>HUVEC</cell_type> and that <protein>TNF alpha</protein> contributes to this phenomenon .


Engagement of the Lewis X antigen ( CD15 ) results in monocyte activation .


We previously reported that monocyte adhesion to tumor necrosis factor-alpha ( TNF-alpha ) -treated endothelial cells increased expression of tissue factor and CD36 on monocytes .

We previously reported that monocyte adhesion to <cell_line>tumor necrosis factor-alpha ( TNF-alpha ) -treated endothelial cells</cell_line> increased expression of tissue factor and <protein>CD36</protein> on monocytes .


Using immunological cross-linking to mimic receptor engagement by natural ligands , we now show that CD15 ( Lewis X ) , a monocyte counter-receptor for endothelial selectins may participate in this response .

Using immunological cross-linking to mimic receptor engagement by natural ligands , we now show that CD15 ( Lewis X ) , a <protein>monocyte counter-receptor</protein> for <protein>endothelial selectins</protein> may participate in this response .


We used cytokine production as a readout for monocyte activation and found that CD15 cross-linking induced TNF-alpha release from peripheral blood monocytes and cells from the monocytic cell line MM6 .

We used cytokine production as a readout for monocyte activation and found that CD15 cross-linking induced <protein>TNF-alpha</protein> release from <cell_type>peripheral blood monocytes</cell_type> and cells from the <cell_line>monocytic cell line MM6</cell_line> .


Quantitative reverse transcriptase -polymerase chain reaction ( RT-PCR ) showed an increase in steady-state TNF-alpha mRNA after 3 to 4 hours of cross-linking .

Quantitative <protein>reverse transcriptase</protein> -polymerase chain reaction ( RT-PCR ) showed an increase in steady-state <rna>TNF-alpha mRNA</rna> after 3 to 4 hours of cross-linking .


CD15 cross-linking also concomitantly increased interleukin-1 beta ( IL-1 beta ) mRNA , while no apparent change was observed in the levels of beta-actin mRNA , indicating specificity .

CD15 cross-linking also concomitantly increased <rna>interleukin-1 beta ( IL-1 beta ) mRNA</rna> , while no apparent change was observed in the levels of <rna>beta-actin mRNA</rna> , indicating specificity .


To examine transcriptional regulation of cytokine genes by CD15 engagement , a CAT plasmid reporter construct containing IL-1 beta promoter/enhancer sequences was introduced into MM6 .

To examine transcriptional regulation of <dna>cytokine genes</dna> by CD15 engagement , a CAT plasmid reporter construct containing <dna>IL-1 beta promoter/enhancer sequences</dna> was introduced into <cell_line>MM6</cell_line> .


Subsequent cross-linking of CD15 increased CAT activity .

Subsequent cross-linking of CD15 increased <protein>CAT</protein> activity .


CD15 engagement by monoclonal antibody also attenuated IL-1 beta transcript degradation , demonstrating that signaling via CD15 also had posttranscriptional effects .

CD15 engagement by <protein>monoclonal antibody</protein> also attenuated <protein>IL-1 beta</protein> transcript degradation , demonstrating that signaling via CD15 also had posttranscriptional effects .


Nuclear extracts of anti- CD15 cross-linked cells demonstrated enhanced levels of the transcriptional factor activator protein-1 , minimally changed nuclear factor-kappa B , and did not affect SV40 promoter specific protein-1 .

Nuclear extracts of anti- <cell_type>CD15 cross-linked cells</cell_type> demonstrated enhanced levels of the <protein>transcriptional factor activator protein-1</protein> , minimally changed <protein>nuclear factor-kappa B</protein> , and did not affect <protein>SV40 promoter specific protein-1</protein> .


We conclude that engagement of CD15 on monocytes results in monocyte activation .


In addition to its well-recognized adhesive role , CD15 may function as an important signaling molecule capable of initiating proinflammatory events in monocytes that come into contact with activated endothelium .

In addition to its well-recognized adhesive role , CD15 may function as an important signaling molecule capable of initiating proinflammatory events in <cell_type>monocytes</cell_type> that come into contact with activated endothelium .


CD2 signalling induces phosphorylation of CREB in primary lymphocytes .

<protein>CD2</protein> signalling induces phosphorylation of <protein>CREB</protein> in <cell_type>primary lymphocytes</cell_type> .


Promoter sequences responsive to cyclic AMP ( cAMP ) are found in a number of cellular genes , and bind transcription factors of the cAMP response element binding protein ( CREB ) /activating transcription factor-1 ( ATF-1 ) family .

Promoter sequences responsive to cyclic AMP ( cAMP ) are found in a number of <dna>cellular genes</dna> , and bind <protein>transcription factors</protein> of the <protein>cAMP response element binding protein</protein> ( <protein>CREB ) /activating transcription factor-1 ( ATF-1 ) family</protein> .


We have used a human T-lymphotropic virus type 1 ( HTLV-1 ) model of cAMP response element ( CRE ) transcription to investigate the influence of lymphocyte activation on transcription from homologous regions in the viral promoter .

We have used a human T-lymphotropic virus type 1 ( HTLV-1 ) model of <dna>cAMP response element</dna> ( <dna>CRE</dna> ) transcription to investigate the influence of lymphocyte activation on transcription from homologous regions in the <dna>viral promoter</dna> .


We previously demonstrated increased HTLV-1 transcription following CD2 but not CD3 receptor cross-linking .


We hypothesized that this increased viral transcription was mediated , in part , through the phosphorylation of CREB .

We hypothesized that this increased viral transcription was mediated , in part , through the phosphorylation of <protein>CREB</protein> .


Therefore , we investigated CD2 and CD3 receptor -mediated signalling in primary human peripheral blood mononuclear cells ( PBMC ) .

Therefore , we investigated <protein>CD2</protein> and <protein>CD3 receptor</protein> -mediated signalling in <cell_type>primary human peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) .


CD2 , but not CD3 , cross-linking increased cAMP detected by competitive enzyme-linked immunosorbent assay ( ELISA ) approximately fourfold .

<protein>CD2</protein> , but not <protein>CD3</protein> , cross-linking increased cAMP detected by competitive enzyme-linked immunosorbent assay ( ELISA ) approximately fourfold .


CD2 cross-linking concurrently increased phosphorylation of CREB detected by immunoblot assay eightfold .

<protein>CD2</protein> cross-linking concurrently increased phosphorylation of <protein>CREB</protein> detected by immunoblot assay eightfold .


Consistent with post-translational regulation , no change in total level of CREB protein was observed .

Consistent with post-translational regulation , no change in total level of <protein>CREB</protein> protein was observed .


Phosphorylation of CREB occurred through a herbimycin A and Rp-cAMP- sensitive pathway , suggesting phosphorylation required antecedent activation of both protein tyrosine kinases ( PTK ) and protein kinase A ( PKA ) .

Phosphorylation of <protein>CREB</protein> occurred through a herbimycin A and Rp-cAMP- sensitive pathway , suggesting phosphorylation required antecedent activation of both <protein>protein tyrosine kinases</protein> ( <protein>PTK</protein> ) and <protein>protein kinase A</protein> ( <protein>PKA</protein> ) .


Both CD2 and CD3 cross-linking increased binding of nuclear proteins to a radiolabelled CRE oligonucleotide probe in electrophoretic mobility shift assays suggesting that lymphocyte activation enhances binding independently of phosphorylation of CREB at serine 133 .

Both <protein>CD2</protein> and <protein>CD3</protein> cross-linking increased binding of <protein>nuclear proteins</protein> to a radiolabelled CRE oligonucleotide probe in electrophoretic mobility shift assays suggesting that lymphocyte activation enhances binding independently of phosphorylation of <protein>CREB</protein> at serine 133 .


These data indicate specific modulation of the CREB/ATF-1 family of transcription factors by the CD2 signalling pathway and suggest CD2 receptor modulation of CRE -mediated transcription following ligand engagement ( e.g. cell-to-cell contact ) .

These data indicate specific modulation of the <protein>CREB/ATF-1 family</protein> of <protein>transcription factors</protein> by the <protein>CD2</protein> signalling pathway and suggest <protein>CD2</protein> receptor modulation of <dna>CRE</dna> -mediated transcription following ligand engagement ( e.g. cell-to-cell contact ) .


X-rays-induced secretion of cellular factor ( s ) that enhance ( s ) HIV-1 promoter transcription in various non-irradiated transfected cell lines .

X-rays-induced secretion of <protein>cellular factor</protein> ( s ) that enhance ( s ) <dna>HIV-1 promoter</dna> transcription in various <cell_line>non-irradiated transfected cell lines</cell_line> .


Various cellular stress agents like ionizing radiation exposure could activate human immunodeficiency virus type 1 ( HIV- 1 ) replication or reporter gene expression .

Various cellular stress agents like ionizing radiation exposure could activate human immunodeficiency virus type 1 ( HIV- 1 ) replication or <dna>reporter gene</dna> expression .


In addition , extracellular factor ( s ) released by X-ray-treated human colonic carcinoma cell line ( HT29 ) might activate the long terminal repeat ( LTR ) of HIV-1 in non-irradiated HT29 cells .

In addition , <protein>extracellular factor</protein> ( s ) released by <cell_line>X-ray-treated human colonic carcinoma cell line</cell_line> ( <cell_line>HT29</cell_line> ) might activate the <dna>long terminal repeat</dna> ( <dna>LTR</dna> ) of HIV-1 in <cell_line>non-irradiated HT29 cells</cell_line> .


In the present report we show that in various transiently or stably transfected cell lines , X-ray irradiation up-regulates HIV-1 LTR transcription through the kappaB regulatory elements .

In the present report we show that in various transiently or <cell_line>stably transfected cell lines</cell_line> , X-ray irradiation up-regulates <dna>HIV-1 LTR</dna> transcription through the <protein>kappaB regulatory elements</protein> .


A factor ( s ) , which is processed by and acts upon a variety of cell types , was detected by addition to non-irradiated cells of either X-ray-treated cells or a conditioned medium taken from irradiated cultures .

A factor ( s ) , which is processed by and acts upon a variety of cell types , was detected by addition to <cell_type>non-irradiated cells</cell_type> of either <cell_line>X-ray-treated cells</cell_line> or a conditioned medium taken from <cell_line>irradiated cultures</cell_line> .


The magnitude of responsiveness is cell type dependent .


In addition , X-ray activation of HIV-1 LTR in transiently or stably transfected cell lines is inhibited by a potent antioxidant drug , pyrrolidine dithiocarbamate and by another drug , known for its role in the trapping of growth factors , suramin .

In addition , X-ray activation of <dna>HIV-1 LTR</dna> in transiently or stably transfected <cell_line>cell lines</cell_line> is inhibited by a potent antioxidant drug , pyrrolidine dithiocarbamate and by another drug , known for its role in the trapping of <protein>growth factors</protein> , suramin .


The importance of these observations in the pathophysiology of patients with AIDS-related cancers treated by radiotherapy remains to be established .


Activation of the human delta-globin gene promoter in primary adult erythroid cells .

Activation of the <dna>human delta-globin gene promoter</dna> in <cell_type>primary adult erythroid cells</cell_type> .


Restoration of the CCAAT box or insertion of an erythroid Kruppel-like factor ( EKLF ) binding site in the delta promoter activates its expression in several erythroid cell lines .

Restoration of the <dna>CCAAT box</dna> or insertion of an <dna>erythroid Kruppel-like factor ( EKLF ) binding site</dna> in the <dna>delta promoter</dna> activates its expression in several <cell_line>erythroid cell lines</cell_line> .


We extended these studies using a novel primary human adult erythroid cell ( hAEC ) system to investigate these effects at the late erythroblast stage .

We extended these studies using a novel <cell_line>primary human adult erythroid cell ( hAEC ) system</cell_line> to investigate these effects at the <cell_type>late erythroblast stage</cell_type> .


Restoration of the CCAAT box at -70 bp , or insertion of an EKLF binding site at -85 bp or -95 bp in the promoter significantly increased delta globin gene expression in hAEC .

Restoration of the <dna>CCAAT box</dna> at <dna>-70 bp</dna> , or insertion of an <dna>EKLF binding site</dna> at <dna>-85 bp</dna> or <dna>-95 bp</dna> in the <dna>promoter</dna> significantly increased delta globin gene expression in hAEC .


Our results demonstrate that the altered CCAAT box ( CCAAC ) and the lack of an EKLF binding site in delta-globin contribute to its low level of expression in the hAEC model as well .

Our results demonstrate that the altered <dna>CCAAT box</dna> ( CCAAC ) and the lack of an <dna>EKLF binding site</dna> in <protein>delta-globin</protein> contribute to its low level of expression in the <cell_line>hAEC model</cell_line> as well .


Constitutive association of JAK1 and STAT5 in pro-B cells is dissolved by interleukin-4 -induced tyrosine phosphorylation of both proteins .

Constitutive association of <protein>JAK1</protein> and <protein>STAT5</protein> in <cell_type>pro-B cells</cell_type> is dissolved by <protein>interleukin-4</protein> -induced tyrosine phosphorylation of both proteins .


The bipartite human interleukin-4 ( IL-4 ) receptor was functionally expressed in murine pro-B cells and activated by human IL-4 to evoke intracellular signaling .

The <protein>bipartite human interleukin-4 ( IL-4 ) receptor</protein> was functionally expressed in <cell_type>murine pro-B cells</cell_type> and activated by <protein>human IL-4</protein> to evoke intracellular signaling .


Mutual association of signal transducing proteins within the receptor complex was then studied in dependence of ligand stimulation .

Mutual association of <protein>signal transducing proteins</protein> within the receptor complex was then studied in dependence of ligand stimulation .


Besides ligand-induced receptor heterodimerization and contacts of the two IL-4 receptor subunits alpha and gamma with Janus kinases JAK1 and JAK3 a prominent constitutive binding between JAK1 and signal transducer and activator of transcription STAT5 was detected .

Besides ligand-induced receptor heterodimerization and contacts of the two <protein>IL-4 receptor subunits alpha and gamma</protein> with <protein>Janus kinases</protein> <protein>JAK1</protein> and <protein>JAK3</protein> a prominent constitutive binding between <protein>JAK1</protein> and <protein>signal transducer and activator of transcription</protein> <protein>STAT5</protein> was detected .


Since both these proteins become phosphorylated in response to IL-4 receptor stimulation , the influence of tyrosine phosphorylation on their mutual contact was analyzed .

Since both these proteins become phosphorylated in response to <protein>IL-4 receptor</protein> stimulation , the influence of tyrosine phosphorylation on their mutual contact was analyzed .


Association of JAK1 and STAT5 was found to occur exclusively between unphosphorylated proteins .

Association of <protein>JAK1</protein> and <protein>STAT5</protein> was found to occur exclusively between <protein>unphosphorylated proteins</protein> .


Activation of human macrophages by mechanical ventilation in vitro .

Activation of <cell_type>human macrophages</cell_type> by mechanical ventilation in vitro .


Positive-pressure mechanical ventilation supports gas exchange in patients with respiratory failure but is also responsible for significant lung injury .


In this study , we have developed an in vitro model in which isolated lung cells can be submitted to a prolonged cyclic pressure-stretching strain resembling that of conventional mechanical ventilation .

In this study , we have developed an in vitro model in which isolated <cell_type>lung cells</cell_type> can be submitted to a <cell_line>prolonged cyclic pressure-stretching strain</cell_line> resembling that of conventional mechanical ventilation .


In this model , cells cultured on a Silastic membrane were elongated up to 7 % of their initial diameter , corresponding to a 12 % increase in cell surface .


The lung macrophage was identified as the main cellular source for critical inflammatory mediators such as tumor necrosis factor-alpha , the chemokines interleukin ( IL ) -8 and -6 , and matrix metalloproteinase-9 in this model system of mechanical ventilation .

The <cell_type>lung macrophage</cell_type> was identified as the main cellular source for critical <protein>inflammatory mediators</protein> such as <protein>tumor necrosis factor-alpha</protein> , the <protein>chemokines</protein> <protein>interleukin ( IL ) -8 and -6</protein> , and <protein>matrix metalloproteinase-9</protein> in this model system of mechanical ventilation .


These mediators were measured in supernatants from ventilated alveolar macrophages , monocyte-derived macrophages , and promonocytic THP-1 cells .

These mediators were measured in supernatants from <cell_type>ventilated alveolar macrophages</cell_type> , <cell_type>monocyte-derived macrophages</cell_type> , and <cell_line>promonocytic THP-1 cells</cell_line> .


Nuclear factor-kappaB was found to be activated in ventilated macrophages .

<protein>Nuclear factor-kappaB</protein> was found to be activated in <cell_type>ventilated macrophages</cell_type> .


Synergistic proinflammatory effects of mechanical stress and molecules such as bacterial endotoxin were observed , suggesting that mechanical ventilation might be particularly deleterious in preinjured or infected lungs .

Synergistic proinflammatory effects of mechanical stress and molecules such as <protein>bacterial endotoxin</protein> were observed , suggesting that mechanical ventilation might be particularly deleterious in preinjured or infected lungs .


Dexamethasone prevented IL-8 and tumor necrosis factor-alpha secretion in ventilated macrophages .

Dexamethasone prevented <protein>IL-8</protein> and <protein>tumor necrosis factor-alpha</protein> secretion in <cell_type>ventilated macrophages</cell_type> .


Mechanical ventilation induced low levels of IL-8 secretion by alveolar type II-like cells .

Mechanical ventilation induced low levels of <protein>IL-8</protein> secretion by <cell_type>alveolar type II-like cells</cell_type> .


Other lung cell types such as endothelial cells , bronchial cells , and fibroblasts failed to produce IL-8 in response to a prolonged cyclic pressure-stretching load .

Other lung cell types such as <cell_type>endothelial cells</cell_type> , <cell_type>bronchial cells</cell_type> , and <cell_type>fibroblasts</cell_type> failed to produce <protein>IL-8</protein> in response to a prolonged cyclic pressure-stretching load .


This model is of particular value for exploring physical stress-induced signaling pathways , as well as for testing the effects of novel ventilatory strategies or adjunctive substances aimed at modulating cell activation induced by mechanical ventilation .


Signaling pathways mediated by the TNF- and cytokine-receptor families target a common cis-element of the IFN regulatory factor 1 promoter .

Signaling pathways mediated by the <protein>TNF- and cytokine-receptor</protein> families target a common <dna>cis-element</dna> of the <dna>IFN regulatory factor 1 promoter</dna> .


CD40 activation of B cells is strongly influenced by the presence of cytokines .

<protein>CD40</protein> activation of <cell_type>B cells</cell_type> is strongly influenced by the presence of <protein>cytokines</protein> .


However , the molecular basis for the interplay between these distinct stimuli is not clearly delineated .


IFN regulatory factor 1 ( IRF-1 ) is a transcription factor activated by either CD40 or cytokines .

<protein>IFN regulatory factor 1</protein> ( <protein>IRF-1</protein> ) is a <protein>transcription factor</protein> activated by either <protein>CD40</protein> or <protein>cytokines</protein> .


We have found that these different sets of signals target a common cis-acting element in the promoter of this gene , the IRF-1 gamma-activated site ( GAS ) .

We have found that these different sets of signals target a common cis-acting element in the promoter of this gene , the <dna>IRF-1 gamma-activated site</dna> ( <dna>GAS</dna> ) .


Targeting of the IRF-1 GAS is not confined to activation via CD40 but extends to other stimuli that mimic the CD40 signaling cascade , like TNF-alpha and EBV .

Targeting of the <dna>IRF-1 GAS</dna> is not confined to activation via <protein>CD40</protein> but extends to other stimuli that mimic the <protein>CD40</protein> signaling cascade , like <protein>TNF-alpha</protein> and EBV .


In contrast to induction of STATs by cytokines , the IRF-1 GAS -binding complex activated by CD40 , TNF-alpha , or EBV contains Rel proteins , specifically p50 and p65 .

In contrast to induction of <protein>STATs</protein> by <protein>cytokines</protein> , the <dna>IRF-1 GAS</dna> -binding complex activated by <protein>CD40</protein> , <protein>TNF-alpha</protein> , or EBV contains <protein>Rel proteins</protein> , specifically <protein>p50</protein> and <protein>p65</protein> .


In this system , simultaneous exposure to CD40L together with either IL-4 or IFN-gamma does not lead to the activation of novel Rel/STAT complexes .

In this system , simultaneous exposure to <protein>CD40L</protein> together with either <protein>IL-4</protein> or <protein>IFN-gamma</protein> does not lead to the activation of novel <protein>Rel/STAT complexes</protein> .


Given the importance of IRF-1 in a variety of biologic functions from proliferation to apoptosis , our findings support the notion that modulation of IRF-1 levels may be a critical control point in B cell activation .

Given the importance of <protein>IRF-1</protein> in a variety of biologic functions from proliferation to apoptosis , our findings support the notion that modulation of <protein>IRF-1</protein> levels may be a critical control point in B cell activation .


Differential effects of protein kinase C inhibitors on fibronectin -induced interleukin-beta gene transcription , protein synthesis and secretion in human monocytic cells .

Differential effects of <protein>protein kinase C</protein> inhibitors on <protein>fibronectin</protein> -induced <dna>interleukin-beta gene</dna> transcription , protein synthesis and secretion in <cell_type>human monocytic cells</cell_type> .


Human monocytic cells express interleukin-1beta ( IL-1beta ) when stimulated with the extracellular matrix glycoprotein , fibronectin ( FN ) .

<cell_type>Human monocytic cells</cell_type> express <protein>interleukin-1beta</protein> ( <protein>IL-1beta</protein> ) when stimulated with the <protein>extracellular matrix glycoprotein</protein> , <protein>fibronectin</protein> ( <protein>FN</protein> ) .


Protein kinase C ( PKC ) activation is considered important for this process ; however , the metabolic steps at which PKC acts upon to mediate the FN -induced IL-1beta response remain unclear .

<protein>Protein kinase C</protein> ( <protein>PKC</protein> ) activation is considered important for this process ; however , the metabolic steps at which <protein>PKC</protein> acts upon to mediate the <protein>FN</protein> -induced <protein>IL-1beta</protein> response remain unclear .