B-cell-specific transcription of immunoglobulin genes is mediated by the interaction of a POU domain containing transcription factor Oct-1 or Oct-2 , with the B-cell-specific coactivator OCA-B ( Bob-1 , OBF-1 ) and a prototype octamer element .

B-cell-specific transcription of <dna>immunoglobulin genes</dna> is mediated by the interaction of a <dna>POU domain</dna> containing <protein>transcription factor</protein> <protein>Oct-1</protein> or <protein>Oct-2</protein> , with the <protein>B-cell-specific coactivator</protein> <protein>OCA-B</protein> ( <protein>Bob-1</protein> , <protein>OBF-1</protein> ) and a <dna>prototype octamer element</dna> .


We find that OCA-B binds DNA directly in the major groove between the two subdomains of the POU domain , requiring both an A at the fifth position of the octamer element and contact with the POU domain .

We find that <protein>OCA-B</protein> binds DNA directly in the major groove between the two subdomains of the <dna>POU domain</dna> , requiring both an A at the <dna>fifth position</dna> of the <dna>octamer element</dna> and contact with the <dna>POU domain</dna> .


An amino-terminal fragment of OCA-B binds the octamer site in the absence of a POU domain with the same sequence specificity .

An <protein>amino-terminal fragment</protein> of <protein>OCA-B</protein> binds the <dna>octamer site</dna> in the absence of a <dna>POU domain</dna> with the same sequence specificity .


Coactivator OCA-B may undergo a POU-dependent conformational change that exposes its amino terminus , allowing it to recognize specific DNA sequences in the major groove within the binding site for Oct-1 or Oct-2 .

Coactivator <protein>OCA-B</protein> may undergo a POU-dependent conformational change that exposes its amino terminus , allowing it to recognize specific <dna>DNA sequences</dna> in the major groove within the binding site for <protein>Oct-1</protein> or <protein>Oct-2</protein> .


The recognition of both the POU domain and the octamer sequence by OCA-B provides a mechanism for differential regulation of octamer sites containing genes by the ubiquitous factor Oct-1 .

The recognition of both the <dna>POU domain</dna> and the <dna>octamer sequence</dna> by <protein>OCA-B</protein> provides a mechanism for differential regulation of <dna>octamer sites</dna> containing genes by the <protein>ubiquitous factor</protein> <protein>Oct-1</protein> .


Uneven X inactivation in a female monozygotic twin pair with Fabry disease and discordant expression of a novel mutation in the alpha-galactosidase A gene .

Uneven <dna>X</dna> inactivation in a female monozygotic twin pair with Fabry disease and discordant expression of a novel mutation in the <dna>alpha-galactosidase A gene</dna> .


We describe two female monozygotic ( MZ ) twins heterozygous for Fabry disease , an X linked disorder resulting from the deficient activity of alpha-galactosidase A .

We describe two female monozygotic ( MZ ) twins heterozygous for Fabry disease , an X linked disorder resulting from the deficient activity of <protein>alpha-galactosidase A</protein> .


While one of the twins was clinically affected , the other was asymptomatic .


Enzymatic assay of alpha-galactosidase in blood leucocytes , skin fibroblasts , Epstein-Barr virus transformed lymphoid cell lines , and hair follicles of the twins and their parents confirmed the heterozygous status of the twins and indicated that Fabry disease had occurred as a result of a de novo mutation .

Enzymatic assay of <protein>alpha-galactosidase</protein> in <cell_type>blood leucocytes</cell_type> , <cell_type>skin fibroblasts</cell_type> , <cell_line>Epstein-Barr virus transformed lymphoid cell lines</cell_line> , and hair follicles of the twins and their parents confirmed the heterozygous status of the twins and indicated that Fabry disease had occurred as a result of a de novo mutation .


The son of the unaffected twin sister was shown to be hemizygous .


Molecular analysis of the alpha-galactosidase A gene permitted the identification of an as yet undescribed point mutation at position 10182 of exon 5 which causes an Asp to Asn substitution at codon 231 .

Molecular analysis of the <dna>alpha-galactosidase A gene</dna> permitted the identification of an as yet undescribed point mutation at <dna>position 10182 of exon 5</dna> which causes an Asp to Asn substitution at <dna>codon 231</dna> .


Single strand conformation polymorphism ( SSCP ) analysis again showed the heterozygous status of the twins and a normal pattern in their parents .


The basis for the discordant expression of this d novo mutation in the twins was investigated by studying their X inactivation status .


Analysis of the inactive X specific methylation at the androgen receptor gene showed unbalanced inactivation in the twins ' fibroblasts and in opposite directions .

Analysis of the <dna>inactive X</dna> specific methylation at the <dna>androgen receptor gene</dna> showed unbalanced inactivation in the twins ' fibroblasts and in opposite directions .


While the maternally derived X chromosome was preferentially active in the asymptomatic twin , the paternal X chromosome was active in the other , affected twin and was found in her hemizygotic nephew .

While the <dna>maternally derived X chromosome</dna> was preferentially active in the asymptomatic twin , the <dna>paternal X chromosome</dna> was active in the other , affected twin and was found in her hemizygotic nephew .


These data suggest that the paternal X chromosome carries the de novo alpha-galactosidase A mutation and that uneven X inactivation is the underlying mechanism for disease expression in this novel female MZ twin pair .

These data suggest that the <dna>paternal X chromosome</dna> carries the de novo <protein>alpha-galactosidase A</protein> mutation and that uneven X inactivation is the underlying mechanism for disease expression in this novel female MZ twin pair .


This is the first documented case of female twins discordant for Fabry disease .


Precise alignment of sites required for mu enhancer activation in B cells .

Precise <dna>alignment of sites</dna> required for <dna>mu enhancer</dna> activation in <cell_type>B cells</cell_type> .


The lymphocyte-specific immunoglobulin mu heavy-chain gene intronic enhancer is regulated by multiple nuclear factors .

The <dna>lymphocyte-specific immunoglobulin mu heavy-chain gene intronic enhancer</dna> is regulated by multiple <protein>nuclear factors</protein> .


The previously defined minimal enhancer containing the muA , muE3 , and muB sites is transactivated by a combination of the ETS-domain proteins PU.1 and Ets-1 in nonlymphoid cells .

The previously defined <dna>minimal enhancer</dna> containing the <dna>muA , muE3 , and muB sites</dna> is transactivated by a combination of the <protein>ETS-domain proteins</protein> <protein>PU.1</protein> and <protein>Ets-1</protein> in <cell_type>nonlymphoid cells</cell_type> .


The core GGAAs of the muA and muB sites are separated by 30 nucleotides , suggesting that ETS proteins bind to these sites from these same side of the DNA helix .

The core GGAAs of the <dna>muA and muB sites</dna> are separated by 30 nucleotides , suggesting that <protein>ETS proteins</protein> bind to these sites from these same side of the DNA helix .


We tested the necessity for appropriate spatial alignment of these elements by using mutated enhancers with altered spacings .

We tested the necessity for appropriate spatial alignment of these <dna>elements</dna> by using <dna>mutated enhancers</dna> with altered spacings .


A 4- or 10-bp insertion between muE3 and muB inactivated the mu enhancer in S194 plasma cells but did not affect in vitro binding of Ets-1 , PU.1 , or the muE3-binding protein TFE3 , alone or in pairwise combinations .

A 4- or 10-bp insertion between <dna>muE3</dna> and <dna>muB</dna> inactivated the <dna>mu enhancer</dna> in <cell_line>S194 plasma cells</cell_line> but did not affect in vitro binding of Ets-1 , <protein>PU.1</protein> , or the <protein>muE3-binding protein</protein> <protein>TFE3</protein> , alone or in pairwise combinations .


Circular permutation and phasing analyses demonstrated that PU.1 binding but not TFE3 or Ets-1 bends mu enhancer DNA toward the major groove .

Circular permutation and phasing analyses demonstrated that <protein>PU.1</protein> binding but not <protein>TFE3</protein> or <protein>Ets-1</protein> bends <dna>mu enhancer DNA</dna> toward the major groove .


We propose that the requirement for precise spacing of the muA and muB elements is due in part to a directed DNA bend induced by PU.1 .

We propose that the requirement for precise spacing of the <dna>muA and muB elements</dna> is due in part to a directed DNA bend induced by <protein>PU.1</protein> .


[ Cortisone-resistant bronchial asthma ]


There is general agreement on the inflammatory pathogenesis of bronchial asthma : an accumulation of activated eosinophils , degranulated mast cells , T lymphocytes and in very severe forms , granulocytes has constantly been found in the bronchial mucosa .

There is general agreement on the inflammatory pathogenesis of bronchial asthma : an accumulation of <cell_type>activated eosinophils</cell_type> , <cell_type>degranulated mast cells</cell_type> , <cell_type>T lymphocytes</cell_type> and in very severe forms , <cell_type>granulocytes</cell_type> has constantly been found in the bronchial mucosa .


In allergic bronchial asthma , inflammation seems to be orchestrated predominantly by a subset of T lymphocytes , with a phenotype similar to the Th2 subset able to produce IL-4 and IL-5 .

In allergic bronchial asthma , inflammation seems to be orchestrated predominantly by a subset of <cell_type>T lymphocytes</cell_type> , with a phenotype similar to the <cell_type>Th2 subset</cell_type> able to produce <protein>IL-4</protein> and <protein>IL-5</protein> .


Although corticosteroids are the most potent therapeutic agents used for this disease , their anti-inflammatory effect differs from patient to patient .


Some criteria which can be used to define steroid-resistant bronchial asthma are listed here .


This review analyzes various molecular alterations responsible for the deficient response to corticosteroid treatment observed in steroid-resistant bronchial asthmatic subjects .


New knowledge on the mechanism of steroid resistance may have important implications for the treatment of chronic asthma and other diseases .


Mechanisms of transactivation by nuclear factor of activated T cells-1 .

Mechanisms of transactivation by <protein>nuclear factor of activated T cells-1</protein> .


Nuclear factor of activated T cells-family proteins ( NFAT1/NFATp , NFATc , NFAT3 , and NFAT4/NFATx/NFATc3 ) play a key role in the transcription of cytokine genes and other genes during the immune response .

<protein>Nuclear factor of activated T cells-family proteins</protein> ( <protein>NFAT1/NFATp</protein> , <protein>NFATc</protein> , <protein>NFAT3</protein> , and <protein>NFAT4/NFATx/NFATc3</protein> ) play a key role in the transcription of <dna>cytokine genes</dna> and other genes during the immune response .


We have defined the mechanisms of transactivation by NFAT1 .

We have defined the mechanisms of transactivation by <protein>NFAT1</protein> .


NFAT1 possesses two transactivation domains whose sequences are not conserved in the other NFAT-family proteins , and a conserved DNA-binding domain that mediates the recruitment of cooperating nuclear transcription factors even when it is expressed in the absence of other regions of the protein .

<protein>NFAT1</protein> possesses two <dna>transactivation domains</dna> whose sequences are not conserved in the other <protein>NFAT-family proteins</protein> , and a conserved <dna>DNA-binding domain</dna> that mediates the recruitment of cooperating <protein>nuclear transcription factors</protein> even when it is expressed in the absence of other regions of the protein .


The activity of the NH2-terminal transactivation domain is modulated by an adjacent regulatory region that contains several conserved sequence motifs represented only in the NFAT family .

The activity of the <protein>NH2-terminal transactivation domain</protein> is modulated by an adjacent <protein>regulatory region</protein> that contains several <dna>conserved sequence motifs</dna> represented only in the <protein>NFAT family</protein> .


Our results emphasize the multiple levels at which NFAT-dependent transactivation is regulated , and predict significant differences in the architecture of cooperative transcription complexes containing different NFAT-family proteins .

Our results emphasize the multiple levels at which NFAT-dependent transactivation is regulated , and predict significant differences in the architecture of cooperative <protein>transcription complexes</protein> containing different <protein>NFAT-family proteins</protein> .


Induction of activator protein ( AP ) -1 and nuclear factor-kappaB by CD28 stimulation involves both phosphatidylinositol 3-kinase and acidic sphingomyelinase signals .

Induction of <protein>activator protein ( AP ) -1</protein> and <protein>nuclear factor-kappaB</protein> by <protein>CD28</protein> stimulation involves both <protein>phosphatidylinositol 3-kinase</protein> and <protein>acidic sphingomyelinase</protein> signals .


A major obstacle in understanding the signaling events that follow CD28 receptor ligation arises from the fact that CD28 acts as a costimulus to TCR engagement , making it difficult to assess the relative contribution of CD28 signals as distinct from those of the TCR .

A major obstacle in understanding the signaling events that follow <protein>CD28</protein> receptor ligation arises from the fact that <protein>CD28</protein> acts as a costimulus to <protein>TCR</protein> engagement , making it difficult to assess the relative contribution of <protein>CD28</protein> signals as distinct from those of the <protein>TCR</protein> .


To overcome this problem , we have exploited the observation that activated human T cell blasts can be stimulated via the CD28 surface molecule in the absence of antigenic challenge ; thus , we have been able to observe the response of normal T cells to CD28 activation in isolation .

To overcome this problem , we have exploited the observation that activated <cell_type>human T cell blasts</cell_type> can be stimulated via the <protein>CD28 surface molecule</protein> in the absence of antigenic challenge ; thus , we have been able to observe the response of <cell_type>normal T cells</cell_type> to <protein>CD28</protein> activation in isolation .


Using this system , we observed that CD28 stimulation by B7-transfected CHO cells induced a proliferative response in T cells that was not accompanied by measurable IL-2 production .

Using this system , we observed that <protein>CD28</protein> stimulation by <cell_line>B7-transfected CHO cells</cell_line> induced a proliferative response in <cell_type>T cells</cell_type> that was not accompanied by measurable <protein>IL-2</protein> production .


However , subsequent analysis of transcription factor generation revealed that B7 stimulation induced both activator protein-1 ( AP-1 ) and nuclear factor-kappaB ( NF-kappaB ) complexes , but not NF-AT .

However , subsequent analysis of <protein>transcription factor</protein> generation revealed that B7 stimulation induced both <protein>activator protein-1</protein> ( <protein>AP-1</protein> ) and <protein>nuclear factor-kappaB ( NF-kappaB ) complexes</protein> , but not <protein>NF-AT</protein> .


In contrast , engagement of the TCR by class II MHC/superantigen , either with or without CD28 ligation , resulted in the induction of NF-AT , AP-1 , and NF-kappaB as well as IL-2 production .

In contrast , engagement of the <protein>TCR</protein> by <protein>class II MHC/superantigen</protein> , either with or without <protein>CD28</protein> ligation , resulted in the induction of <protein>NF-AT</protein> , <protein>AP-1</protein> , and <protein>NF-kappaB</protein> as well as <protein>IL-2</protein> production .


Using selective inhibitors , we investigated the signaling pathways involved in the CD28 -mediated induction of AP-1 and NF-kappaB .

Using selective inhibitors , we investigated the signaling pathways involved in the <protein>CD28</protein> -mediated induction of <protein>AP-1</protein> and <protein>NF-kappaB</protein> .


This revealed that NF-kappaB generation was sensitive to chloroquine , an inhibitor of acidic sphingomyelinase , but not to the phosphatidylinositol 3-kinase inhibitor , wortmannin .

This revealed that <protein>NF-kappaB</protein> generation was sensitive to chloroquine , an inhibitor of <protein>acidic sphingomyelinase</protein> , but not to the <protein>phosphatidylinositol 3-kinase</protein> inhibitor , wortmannin .


In contrast , AP-1 generation was inhibited by wortmannin and was also variably sensitive to chloroquine .

In contrast , <protein>AP-1</protein> generation was inhibited by wortmannin and was also variably sensitive to chloroquine .


These data suggest that in activated normal T cells , CD28 -derived signals can stimulate proliferation at least in part via NF-kappaB and AP-1 generation , and that this response uses both acidic sphingomyelinase and phosphatidylinositol 3-kinase -linked pathways .

These data suggest that in activated <cell_type>normal T cells</cell_type> , <protein>CD28</protein> -derived signals can stimulate proliferation at least in part via NF-kappaB and AP-1 generation , and that this response uses both <protein>acidic sphingomyelinase</protein> and <protein>phosphatidylinositol 3-kinase</protein> -linked pathways .


Presence of a variant form of the estrogen receptor in peripheral blood mononuclear cells from normal individuals and lupus patients .

Presence of a variant form of the <protein>estrogen receptor</protein> in <cell_type>peripheral blood mononuclear cells</cell_type> from normal individuals and lupus patients .


Estrogen may participate in the pathogenesis of systemic lupus erythematosus ( SLE ) via its intracellular receptor .

Estrogen may participate in the pathogenesis of systemic lupus erythematosus ( SLE ) via its <protein>intracellular receptor</protein> .


To investigate the presence of various isoforms of the estrogen receptor ( ER ) in SLE we isolated RNA from mononuclear cells of lupus patients and normal controls .

To investigate the presence of various isoforms of the <protein>estrogen receptor</protein> ( <protein>ER</protein> ) in SLE we isolated RNA from <cell_type>mononuclear cells</cell_type> of lupus patients and normal controls .


Using RT-PCR we were able to identify both the full length wild-type form and an isoform of the ER which precisely lacks exon V in both patient and normal individuals .

Using RT-PCR we were able to identify both the <protein>full length wild-type form</protein> and an isoform of the <protein>ER</protein> which precisely lacks <dna>exon V</dna> in both patient and normal individuals .


Our results , although limited , suggest that normal individuals can express both the wild-type and truncated version at the same time , whereas lupus patients only express either the wild-type or the truncated ER .

Our results , although limited , suggest that normal individuals can express both the wild-type and truncated version at the same time , whereas lupus patients only express either the <protein>wild-type or the truncated ER</protein> .


This finding may lead to a better understanding of the reasons for the prevalence of lupus in females and of the estrogenic effects on SLE disease activity .


Regulation of sialoadhesin expression on rat macrophages .

Regulation of <protein>sialoadhesin</protein> expression on <cell_type>rat macrophages</cell_type> .


Induction by glucocorticoids and enhancement by IFN-beta , IFN-gamma , IL-4 , and lipopolysaccharide .

Induction by glucocorticoids and enhancement by <protein>IFN-beta</protein> , <protein>IFN-gamma</protein> , <protein>IL-4</protein> , and lipopolysaccharide .


Sialoadhesin is a macrophage-restricted member of the Ig superfamily that mediates adhesion with lymphoid and myeloid cells .

<protein>Sialoadhesin</protein> is a <protein>macrophage-restricted member</protein> of the <protein>Ig superfamily</protein> that mediates adhesion with <cell_type>lymphoid and myeloid cells</cell_type> .


It is expressed on a subpopulation of macrophages in lymphoid tissues and in chronic inflammation ( e.g. , during autoimmune diseases ) .

It is expressed on a subpopulation of <cell_type>macrophages</cell_type> in lymphoid tissues and in chronic inflammation ( e.g. , during autoimmune diseases ) .


We have studied the regulation of sialoadhesin expression in vitro and show that glucocorticoids ( GC ) induce sialoadhesin expression on freshly isolated rat macrophages and the rat macrophage cell line R2 .

We have studied the regulation of <protein>sialoadhesin</protein> expression in vitro and show that glucocorticoids ( GC ) induce <protein>sialoadhesin</protein> expression on freshly isolated <cell_type>rat macrophages</cell_type> and the <cell_line>rat macrophage cell line R2</cell_line> .


The cytokines IFN-beta , IFN-gamma , IL-4 , and LPS , although unable to induce sialoadhesin expression by themselves , were able to enhance GC-mediated induction of sialoadhesin .

The <protein>cytokines</protein> <protein>IFN-beta</protein> , <protein>IFN-gamma</protein> , <protein>IL-4</protein> , and LPS , although unable to induce <protein>sialoadhesin</protein> expression by themselves , were able to enhance GC-mediated induction of <protein>sialoadhesin</protein> .


Sialoadhesin expression was functional as shown by cell adhesion assays with human RBCs .

<protein>Sialoadhesin</protein> expression was functional as shown by cell adhesion assays with <cell_type>human RBCs</cell_type> .


Northern blotting experiments indicated that regulation predominantly occurred at the mRNA level .


Comparison of the different combinations of GC and cytokines /LPS revealed differences in the level of GC-dependent enhancement of sialoadhesin expression , with IFN-beta and IL-4 being more potent than IFN-gamma and LPS .

Comparison of the different combinations of GC and <protein>cytokines</protein> /LPS revealed differences in the level of GC-dependent enhancement of <protein>sialoadhesin</protein> expression , with <protein>IFN-beta</protein> and <protein>IL-4</protein> being more potent than <protein>IFN-gamma</protein> and LPS .


Moreover , the effects of IFN-gamma and LPS could be reproduced by priming , whereas IFN-beta and IL-4 were required simultaneously with GC .

Moreover , the effects of <protein>IFN-gamma</protein> and LPS could be reproduced by priming , whereas <protein>IFN-beta</protein> and <protein>IL-4</protein> were required simultaneously with GC .


The regulation of sialoadhesin expression was mediated by the GC receptor , and not by mineralocorticoid receptor , as shown by inhibition experiments with specific antagonists .

The regulation of <protein>sialoadhesin</protein> expression was mediated by the <protein>GC receptor</protein> , and not by <protein>mineralocorticoid receptor</protein> , as shown by inhibition experiments with specific antagonists .


Finally , it is demonstrated that macrophages in the adrenal gland , the major site of endogenous GC production , express sialoadhesin .

Finally , it is demonstrated that <cell_type>macrophages</cell_type> in the adrenal gland , the major site of endogenous GC production , express <protein>sialoadhesin</protein> .


This study demonstrates that GC act as a primary inducer of sialoadhesin expression on rat macrophages , and that the response can be enhanced by IFN-beta , T cell-derived cytokines , or LPS .

This study demonstrates that GC act as a primary inducer of <protein>sialoadhesin</protein> expression on <cell_type>rat macrophages</cell_type> , and that the response can be enhanced by <protein>IFN-beta</protein> , <protein>T cell-derived cytokines</protein> , or LPS .


Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2 .

Apoptosis mediated by <protein>HIV protease</protein> is preceded by cleavage of <protein>Bcl-2</protein> .


Expression of the human immunodeficiency virus type 1 ( HIV ) protease in cultured cells leads to apoptosis , preceded by cleavage of bcl-2 , a key negative regulator of cell death .

Expression of the <protein>human immunodeficiency virus type 1 ( HIV ) protease</protein> in <cell_line>cultured cells</cell_line> leads to apoptosis , preceded by cleavage of <protein>bcl-2</protein> , a key negative regulator of cell death .


In contrast , a high level of bcl-2 protects cells in vitro and in vivo from the viral protease and prevents cell death following HIV infection of human lymphocytes , while reducing the yields of viral structural proteins , infectivity , and tumor necrosis factor alpha .

In contrast , a high level of <protein>bcl-2</protein> protects cells in vitro and in vivo from the <protein>viral protease</protein> and prevents cell death following HIV infection of <cell_type>human lymphocytes</cell_type> , while reducing the yields of <protein>viral structural proteins</protein> , infectivity , and <protein>tumor necrosis factor alpha</protein> .


We present a model for HIV replication in which the viral protease depletes the infected cells of bcl-2 , leading to oxidative stress-dependent activation of NF kappa B , a cellular factor required for HIV transcription , and ultimately to cell death .

We present a model for HIV replication in which the <protein>viral protease</protein> depletes the infected cells of <protein>bcl-2</protein> , leading to oxidative stress-dependent activation of <protein>NF kappa B</protein> , a <protein>cellular factor</protein> required for HIV transcription , and ultimately to cell death .


Purified bcl-2 is cleaved by HIV protease between phenylalanine 112 and alanine 113 .

Purified <protein>bcl-2</protein> is cleaved by <protein>HIV protease</protein> between phenylalanine 112 and alanine 113 .


The results suggest a new option for HIV gene therapy ; bcl-2 muteins that have noncleavable alterations surrounding the HIV protease cleavage site .

The results suggest a new option for HIV gene therapy ; <protein>bcl-2 muteins</protein> that have <protein>noncleavable alterations</protein> surrounding the <protein>HIV protease cleavage site</protein> .


Alpha 4 beta 1 ( CD49d/CD29 ) integrin costimulation of human T cells enhances transcription factor and cytokine induction in the absence of altered sensitivity to anti-CD3 stimulation .

<protein>Alpha 4 beta 1 ( CD49d/CD29 ) integrin</protein> costimulation of <cell_type>human T cells</cell_type> enhances <protein>transcription factor</protein> and cytokine induction in the absence of altered sensitivity to <protein>anti-CD3</protein> stimulation .


The integrin alpha 4 beta 1 can provide a costimulus to induce IL-2 secretion and IL-2R expression leading to enhanced proliferation of purified , peripheral blood T cells .

The <protein>integrin alpha 4 beta 1</protein> can provide a costimulus to induce <protein>IL-2</protein> secretion and <protein>IL-2R</protein> expression leading to enhanced proliferation of purified , <cell_type>peripheral blood T cells</cell_type> .


Similar to expression of IL-2 , we demonstrated that recombinant vascular-cell adhesion molecule-1 , when co-immobilized with anti-CD3 mAb , significantly enhanced the induction of transcription factors NF-AT , AP-1 , and NF-kappa B as determined by electromobility shift assays .

Similar to expression of <protein>IL-2</protein> , we demonstrated that <protein>recombinant vascular-cell adhesion molecule-1</protein> , when co-immobilized with <protein>anti-CD3 mAb</protein> , significantly enhanced the induction of <protein>transcription factors</protein> <protein>NF-AT</protein> , <protein>AP-1</protein> , and <protein>NF-kappa B</protein> as determined by electromobility shift assays .


alpha 4 beta 1 ligation alone had no effect on transcription factor binding .

<protein>alpha 4 beta 1</protein> ligation alone had no effect on <protein>transcription factor</protein> binding .


The requirements for induction of transcription factors reflected the requirements for the secretion of multiple cytokines , including IL-2 , TNF-alpha , IFN-gamma , and granulocyte macrophage-CSF .

The requirements for induction of <protein>transcription factors</protein> reflected the requirements for the secretion of multiple <protein>cytokines</protein> , including <protein>IL-2</protein> , <protein>TNF-alpha</protein> , <protein>IFN-gamma</protein> , and <protein>granulocyte macrophage-CSF</protein> .


In contrast to freshly isolated T cells , in vitro-cultured T cells did not require costimulation for cytokine secretion in response to anti-CD3 alone .

In contrast to <cell_type>freshly isolated T cells</cell_type> , in <cell_line>vitro-cultured T cells</cell_line> did not require costimulation for <protein>cytokine</protein> secretion in response to <protein>anti-CD3</protein> alone .


Comparison of the dose response to anti-CD3 stimulation demonstrated that half-maximal induction of IL-2 was achieved using the same dose of anti-CD3 for both freshly isolated and cultured T cells .

Comparison of the dose response to <protein>anti-CD3</protein> stimulation demonstrated that half-maximal induction of <protein>IL-2</protein> was achieved using the same dose of <protein>anti-CD3</protein> for both <cell_type>freshly isolated</cell_type> and <cell_line>cultured T cells</cell_line> .


Furthermore , the dose of OKT3 required to achieve half-maximal activation was the same using PMA or different concentrations of alpha 4 beta 1 ligands .

Furthermore , the dose of <protein>OKT3</protein> required to achieve half-maximal activation was the same using PMA or different concentrations of <protein>alpha 4 beta 1</protein> ligands .


Therefore , costimulation by alpha 4 beta 1 ligands was not due to stabilization of the interaction of the cells with its substrate .

Therefore , costimulation by <protein>alpha 4 beta 1</protein> ligands was not due to stabilization of the interaction of the cells with its substrate .


We conclude , rather , that alpha 4 beta 1 in freshly isolated T cells delivers a distinct signal that synergizes early with signals initiated by TCR/CD3 ligation to induce DNA binding of multiple transcription factors required for cytokine gene induction .

We conclude , rather , that <protein>alpha 4 beta 1</protein> in <cell_type>freshly isolated T cells</cell_type> delivers a distinct signal that synergizes early with signals initiated by <protein>TCR/CD3</protein> ligation to induce DNA binding of multiple <protein>transcription factors</protein> required for <dna>cytokine gene</dna> induction .


Inhibition of T lymphocyte activation by cAMP is associated with down-regulation of two parallel mitogen-activated protein kinase pathways , the extracellular signal-related kinase and c-Jun N-terminal kinase .

Inhibition of <cell_type>T lymphocyte</cell_type> activation by cAMP is associated with down-regulation of two parallel mitogen-activated <protein>protein kinase</protein> pathways , the <protein>extracellular signal-related kinase</protein> and <protein>c-Jun N-terminal kinase</protein> .


The induction of T cell proliferation requires signals from the TCR and a co-receptor molecule , such as CD28 , that activate parallel and partially cross-reactive signaling pathways .

The induction of T cell proliferation requires signals from the <protein>TCR</protein> and a <protein>co-receptor molecule</protein> , such as <protein>CD28</protein> , that activate parallel and partially cross-reactive signaling pathways .


These pathways are disrupted by agonists that utilize adenylate cyclase and cAMP-dependent protein kinase A ( PKA ) .

These pathways are disrupted by agonists that utilize <protein>adenylate cyclase</protein> and <protein>cAMP-dependent protein kinase A</protein> ( <protein>PKA</protein> ) .


We found that the adenylate cyclase activator , forskolin , inhibits anti-CD3 -induced shift in Lck electrophoretic mobility , suggesting an intervention at the TCR -coupled phosphoinositide turnover that precedes the activation of PKC .

We found that the <protein>adenylate cyclase</protein> activator , forskolin , inhibits <protein>anti-CD3</protein> -induced shift in <protein>Lck</protein> electrophoretic mobility , suggesting an intervention at the <protein>TCR</protein> -coupled phosphoinositide turnover that precedes the activation of <protein>PKC</protein> .


The shift of Lck following direct PKC activation by 12-O-tetradecanoyl phorbol 13-acetate , which bypasses early receptor-triggered biochemical events , is insensitive to forskolin .

The shift of <protein>Lck</protein> following direct <protein>PKC</protein> activation by 12-O-tetradecanoyl phorbol 13-acetate , which bypasses early receptor-triggered biochemical events , is insensitive to forskolin .


Nevertheless , forskolin also inhibits PKC downstream events , such as c-jun expression , which is critical for the activation process of T cells .

Nevertheless , forskolin also inhibits <protein>PKC</protein> downstream events , such as <dna>c-jun</dna> expression , which is critical for the activation process of <cell_type>T cells</cell_type> .


To further analyze potential cross points between positively and negatively regulating signaling pathways in T cells , we tested the effects of activators of the adenylate cyclase or PKA on two parallel mitogen-activated protein kinase signaling pathways mediated by extracellular signal-regulated kinase ( ERK ) and c-Jun N-terminal kinase .

To further analyze potential cross points between positively and negatively regulating signaling pathways in <cell_type>T cells</cell_type> , we tested the effects of activators of the <protein>adenylate cyclase</protein> or <protein>PKA</protein> on two parallel mitogen-activated protein kinase signaling pathways mediated by <protein>extracellular signal-regulated kinase</protein> ( <protein>ERK</protein> ) and <protein>c-Jun N-terminal kinase</protein> .


Using a PKC -specific inhibitor , GF109203X , or PKC-depleted T cells , we found that a large part of the anti-CD3 -induced ERK activation is PKC dependent .

Using a <protein>PKC</protein> -specific inhibitor , GF109203X , or <cell_line>PKC-depleted T cells</cell_line> , we found that a large part of the <protein>anti-CD3</protein> -induced <protein>ERK</protein> activation is <protein>PKC</protein> dependent .


Both PKC- dependent and -independent activation of ERK were sensitive to inhibition by forskolin or a cell-permeable cAMP analogue , dbcAMP .

Both PKC- dependent and -independent activation of <protein>ERK</protein> were sensitive to inhibition by forskolin or a cell-permeable cAMP analogue , dbcAMP .


Furthermore , the effect of 12-O-tetradecanoyl phorbol 13-acetate and ionomycin , which synergized to fully activate c-Jun N-terminal kinase , was also sensitive to inhibition by forskolin .

Furthermore , the effect of 12-O-tetradecanoyl phorbol 13-acetate and ionomycin , which synergized to fully activate <protein>c-Jun N-terminal kinase</protein> , was also sensitive to inhibition by forskolin .


Our results suggest that PKA inhibits T cell activation by interfering with multiple events along the two signaling pathways operating downstream of the TCR and the CD28 co-receptor molecules .

Our results suggest that <protein>PKA</protein> inhibits T cell activation by interfering with multiple events along the two signaling pathways operating downstream of the <protein>TCR</protein> and the <protein>CD28 co-receptor molecules</protein> .


Transcriptional and posttranscriptional regulation of erythroid gene expression in anthracycline-induced differentiation of human erythroleukemic cells .

Transcriptional and posttranscriptional regulation of <dna>erythroid gene</dna> expression in anthracycline-induced differentiation of <cell_type>human erythroleukemic cells</cell_type> .


Aclacinomycin ( ACLA ) and doxorubicin ( DOX ) were used at subtoxic concentrations to induce erythroid differentiation in the human leukemic cell line K562 .

Aclacinomycin ( ACLA ) and doxorubicin ( DOX ) were used at subtoxic concentrations to induce erythroid differentiation in the <cell_line>human leukemic cell line K562</cell_line> .


Cell hemoglobinization was accompanied by the increased expression of genes encoding gamma-globin and porphobilinogen deaminase ( PBGD ) , an enzyme of heme synthesis .

Cell hemoglobinization was accompanied by the increased expression of <dna>genes</dna> encoding <protein>gamma-globin and porphobilinogen deaminase</protein> ( <protein>PBGD</protein> ) , an enzyme of heme synthesis .


By using run-on assays , ACLA was shown to induce an enhancement of the transcription of erythroid genes , including gamma-globin , PBGD , erythropoietin receptor , and GATA-1 transcription factor .

By using run-on assays , ACLA was shown to induce an enhancement of the transcription of <dna>erythroid genes</dna> , including <protein>gamma-globin</protein> , <protein>PBGD</protein> , <protein>erythropoietin receptor</protein> , and <protein>GATA-1</protein> <protein>transcription factor</protein> .


In contrast , in DOX-treated cells , the transcription rate of these genes was unchanged in comparison with control cells .

In contrast , in <cell_line>DOX-treated cells</cell_line> , the transcription rate of these <dna>genes</dna> was unchanged in comparison with <cell_type>control cells</cell_type> .


In addition , inhibition of mRNA synthesis with actinomycin D indicated that DOX induced an increased stability of PBGD and GATA-1 mRNAs , whereas ACLA did not affect the half-lives of these mRNAs .

In addition , inhibition of <rna>mRNA</rna> synthesis with actinomycin D indicated that DOX induced an increased stability of <rna>PBGD and GATA-1 mRNAs</rna> , whereas ACLA did not affect the half-lives of these <rna>mRNAs</rna> .


Because the increase in erythroid mRNA steady-state level in anthracycline-treated cells was inhibited by cycloheximide , this suggests that transcriptional activation in ACLA-treated cells and mRNA stabilization in DOX-treated cells were dependent on de novo protein synthesis .

Because the increase in <rna>erythroid mRNA</rna> steady-state level in <cell_type>anthracycline-treated cells</cell_type> was inhibited by cycloheximide , this suggests that transcriptional activation in <cell_line>ACLA-treated cells</cell_line> and mRNA stabilization in <cell_type>DOX-treated cells</cell_type> were dependent on de novo protein synthesis .


Finally , GATA-1 protein level was shown to be increased in ACLA-treated but not in DOX-treated cells .

Finally , <protein>GATA-1</protein> protein level was shown to be increased in <cell_line>ACLA-treated but not in DOX-treated cells</cell_line> .


These two anthracyclines , although closely related in their structures , appeared to act as differentiation inducers by distinct mechanisms .


Indeed , erythroid gene expression was demonstrated to be regulated transcriptionally by ACLA and mainly posttranscriptionally by DOX .

Indeed , <dna>erythroid gene</dna> expression was demonstrated to be regulated transcriptionally by ACLA and mainly posttranscriptionally by DOX .


Interleukin-7 signaling in human B cell precursor acute lymphoblastic leukemia cells and murine BAF3 cells involves activation of STAT1 and STAT5 mediated via the interleukin-7 receptor alpha chain .

<protein>Interleukin-7</protein> signaling in <cell_line>human B cell precursor acute lymphoblastic leukemia cells</cell_line> and <cell_line>murine BAF3 cells</cell_line> involves activation of <protein>STAT1</protein> and <protein>STAT5</protein> mediated via the <protein>interleukin-7 receptor alpha chain</protein> .


Interleukin-7 ( IL-7 ) stimulates the proliferation of normal and leukemic B and T cell precursors and T lymphocytes .

<protein>Interleukin-7</protein> ( <protein>IL-7</protein> ) stimulates the proliferation of <cell_type>normal and leukemic B and T cell precursors and T lymphocytes</cell_type> .


Activation of the JAK /STAT pathway has been implicated in IL-7R signaling .

Activation of the <protein>JAK</protein> <protein>/STAT</protein> pathway has been implicated in <protein>IL-7R</protein> signaling .


We investigated which STAT complexes are formed upon stimulation of B cell precursor acute lymphoblastic leukemia ( BCP-ALL ) cells with IL-7 .

We investigated which <protein>STAT complexes</protein> are formed upon stimulation of <cell_line>B cell precursor acute lymphoblastic leukemia ( BCP-ALL ) cells</cell_line> with <protein>IL-7</protein> .


Gel retardation assays with STAT-binding oligonucleotides showed that IL-7 induces the formation of two major STAT complexes in BCP-ALL cells .

Gel retardation assays with STAT-binding oligonucleotides showed that <protein>IL-7</protein> induces the formation of two major <protein>STAT complexes</protein> in <cell_line>BCP-ALL cells</cell_line> .


Supershifts with anti-STAT antibodies identified these as STAT1 and STAT5 complexes .

Supershifts with anti-STAT antibodies identified these as <protein>STAT1</protein> and <protein>STAT5 complexes</protein> .


This pattern of STAT activation was seen in all BCP-ALL cases that respond to IL-7 in proliferation assays .

This pattern of <protein>STAT</protein> activation was seen in all BCP-ALL cases that respond to <protein>IL-7</protein> in proliferation assays .


IL-7 also induced STAT /DNA binding in BCP-ALL cases that failed to proliferate in response to IL-7 , suggesting that the ability of IL-7R to activate the JAK /STAT pathway per se is not sufficient for proliferation induction .

<protein>IL-7</protein> also induced <protein>STAT</protein> /DNA binding in BCP-ALL cases that failed to proliferate in response to <protein>IL-7</protein> , suggesting that the ability of <protein>IL-7R</protein> to activate the <protein>JAK</protein> <protein>/STAT</protein> pathway per se is not sufficient for proliferation induction .


To determine the contribution of the cytoplasmic domain of the IL-7 receptor alpha chain ( IL-7R alpha ) to activation of STAT proteins , transfectants of the murine pro-B cell line BAF3 were made that express chimeric receptors consisting of the extracellular domain of human granulocyte colony-stimulating factor receptor ( G-CSF-R ) and the transmembrane and intracellular domains of human IL-7R alpha .

To determine the contribution of the <protein>cytoplasmic domain</protein> of the <protein>IL-7 receptor alpha chain</protein> ( <protein>IL-7R alpha</protein> ) to activation of <protein>STAT proteins</protein> , transfectants of the <cell_line>murine pro-B cell line BAF3</cell_line> were made that express <protein>chimeric receptors</protein> consisting of the <protein>extracellular domain</protein> of <protein>human granulocyte colony-stimulating factor receptor</protein> ( <protein>G-CSF-R</protein> ) and the <protein>transmembrane and intracellular domains</protein> of <protein>human IL-7R alpha</protein> .


Activation of the chimeric G-CSF-R/IL-7R alpha with G-CSF resulted in a full proliferative response and induced the phosphorylation of JAK1 but not JAK2 .

Activation of the <protein>chimeric G-CSF-R/IL-7R alpha</protein> with <protein>G-CSF</protein> resulted in a full proliferative response and induced the phosphorylation of <protein>JAK1</protein> but not <protein>JAK2</protein> .


Major STAT complexes activated by G-CSF-R/IL-7R alpha contained STAT1 or STAT5 , while some formation of STAT3-containing complexes was also seen .

Major <protein>STAT complexes</protein> activated by <protein>G-CSF-R/IL-7R alpha</protein> contained <protein>STAT1</protein> or <protein>STAT5</protein> , while some formation of <protein>STAT3-containing complexes</protein> was also seen .


These findings establish that STAT1 and STAT5 , and possibly STAT3 , are activated upon stimulation of precursor B cells with IL-7 .

These findings establish that <protein>STAT1</protein> and <protein>STAT5</protein> , and possibly <protein>STAT3</protein> , are activated upon stimulation of <cell_type>precursor B cells</cell_type> with <protein>IL-7</protein> .


The data further indicate that the IL-7R alpha chains are directly involved in the activation of JAKs and STATs and have a major role in proliferative signaling in precursor B cells .

The data further indicate that the <protein>IL-7R alpha chains</protein> are directly involved in the activation of <protein>JAKs</protein> and <protein>STATs</protein> and have a major role in proliferative signaling in <cell_type>precursor B cells</cell_type> .


Stimulation of human lymphocyte proliferation and CD40 antigen expression by phosphorothioate oligonucleotides complementary to hepatitis B virus genome .

Stimulation of human lymphocyte proliferation and <protein>CD40</protein> antigen expression by phosphorothioate oligonucleotides complementary to <dna>hepatitis B virus genome</dna> .


We have studied the proliferation and CD40 antigen expression of lymphocytes , and the cytotoxicity to monocytes , of antisense phosphorothioate oligodeoxynucleotides complementary to the SP II promoter of HBV mRNA ( sequence I ) and the X gene ( sequence II ) in patients with chronic hepatitis B .

We have studied the proliferation and <protein>CD40</protein> antigen expression of <cell_type>lymphocytes</cell_type> , and the cytotoxicity to <cell_type>monocytes</cell_type> , of antisense phosphorothioate oligodeoxynucleotides complementary to the <dna>SP II promoter</dna> of <rna>HBV mRNA</rna> ( sequence I ) and the <dna>X gene</dna> ( sequence II ) in patients with chronic hepatitis B .


The oligo sequence I stimulated proliferation of both T and , to a lesser extent , B cells .

The oligo sequence I stimulated proliferation of both <cell_type>T and , to a lesser extent , B cells</cell_type> .


The percentage of cells expressing CD40 in T and B cell co-cultures increased from 4.2 % to 13.8 % after oligo stimulation in patients , while it increased form 4.7 % to 48.6 % in healthy controls .

The percentage of cells expressing <protein>CD40</protein> in <cell_line>T and B cell co-cultures</cell_line> increased from 4.2 % to 13.8 % after oligo stimulation in patients , while it increased form 4.7 % to 48.6 % in healthy controls .


The sense sequence ( sequence III ) of the X gene also enhanced the expression of CD40 antigen in patients with hepatitis B .

The sense sequence ( sequence III ) of the <dna>X gene</dna> also enhanced the expression of <protein>CD40 antigen</protein> in patients with hepatitis B .


The proportion of CD40 cells ( 26 % ) in a resting B-cell preparation from hepatitis B patients decreased to zero after a 5-day culture with sequence I , but IgG levels in the culture supernatant increased .

The proportion of <cell_line>CD40 cells</cell_line> ( 26 % ) in a <cell_line>resting B-cell preparation</cell_line> from hepatitis B patients decreased to zero after a 5-day culture with sequence I , but IgG levels in the culture supernatant increased .


The cytotoxic properties of monocytes were not influenced by the oligos .

The cytotoxic properties of <cell_type>monocytes</cell_type> were not influenced by the oligos .


These findings indicate that antisense oligos against hepatitis B virus ( HBV ) have mitogenic effects on the proliferation of human lymphocytes in a non-specific manner and may activate T cells to express CD40 antigen .

These findings indicate that antisense oligos against hepatitis B virus ( HBV ) have mitogenic effects on the proliferation of <cell_type>human lymphocytes</cell_type> in a non-specific manner and may activate <cell_type>T cells</cell_type> to express <protein>CD40 antigen</protein> .


Activation protein 1 -dependent transcriptional activation of interleukin 2 gene by Ca2+/calmodulin kinase type IV/Gr .

<protein>Activation protein 1</protein> -dependent transcriptional activation of <dna>interleukin 2 gene</dna> by <protein>Ca2+/calmodulin kinase type IV/Gr</protein> .


The Ca2+/calmodulin-dependent protein kinase ( CaMK ) type IV/Gr is selectively expressed in T lymphocytes and is activated after signaling via the T cell antigen receptor ( TCR ) , indicating that it mediates some of the Ca ( 2+ ) -dependent transcriptional events that follow TCR engagement .

The <protein>Ca2+/calmodulin-dependent protein kinase ( CaMK ) type IV/Gr</protein> is selectively expressed in <cell_type>T lymphocytes</cell_type> and is activated after signaling via the <protein>T cell antigen receptor</protein> ( <protein>TCR</protein> ) , indicating that it mediates some of the Ca ( 2+ ) -dependent transcriptional events that follow <protein>TCR</protein> engagement .


Here we show that CaMKIV/Gr induces the transcription factor activation protein 1 ( AP-1 ) alone or in synergy with T cell mitogens and with the p21ras oncoprotein .

Here we show that <protein>CaMKIV/Gr</protein> induces the <protein>transcription factor activation protein 1</protein> ( <protein>AP-1</protein> ) alone or in synergy with <protein>T cell mitogens</protein> and with the <protein>p21ras oncoprotein</protein> .


CaMKIV/ Gr signaling is associated with transcriptional activation of c-fos but is independent of p21ras or calcineurin .

<protein>CaMKIV/ Gr</protein> signaling is associated with transcriptional activation of <dna>c-fos</dna> but is independent of <dna>p21ras</dna> or <protein>calcineurin</protein> .


AP-1 is an integral component of the nuclear factor of activated T cells ( NFAT ) transcriptional complex , which is required for interleukin 2 gene expression in T cells .

<protein>AP-1</protein> is an integral component of the <protein>nuclear factor of activated T cells ( NFAT ) transcriptional complex</protein> , which is required for <dna>interleukin 2 gene</dna> expression in <cell_type>T cells</cell_type> .


We demonstrate that CaMKIV/Gr reconstitutes the capacity of the cytosolic component of NFAT to direct transcription from NFAT sites in non- T cells .

We demonstrate that <protein>CaMKIV/Gr</protein> reconstitutes the capacity of the cytosolic component of <protein>NFAT</protein> to direct transcription from <dna>NFAT sites</dna> in non- <cell_type>T cells</cell_type> .


These results reveal a central role for CaMKIV/Gr as a Ca ( 2+ ) -regulated activator of gene transcription in T lymphocytes .

These results reveal a central role for <protein>CaMKIV/Gr</protein> as a Ca ( 2+ ) -regulated activator of gene transcription in <cell_type>T lymphocytes</cell_type> .


IL-12 -induced activation of NK and T cells occurs in the absence of immediate-early activation gene expression .

<protein>IL-12</protein> -induced activation of <cell_type>NK and T cells</cell_type> occurs in the absence of <dna>immediate-early activation gene</dna> expression .


The responses of lymphocytes to IL-2 and IL-12 , involving proliferation , differentiation , and cytokine production , are only partially overlapping , and may depend on induced differential expression of specific sets of genes .

The responses of <cell_type>lymphocytes</cell_type> to <protein>IL-2</protein> and <protein>IL-12</protein> , involving proliferation , differentiation , and <protein>cytokine</protein> production , are only partially overlapping , and may depend on induced differential expression of specific sets of <protein>genes</protein> .


Using reverse-transcription PCR differential display , we isolated an mRNA species expressed in IL-2 -but not IL-12-stimulated NK cells .

Using reverse-transcription PCR differential display , we isolated an <rna>mRNA species</rna> expressed in <cell_type>IL-2 -but not IL-12-stimulated NK cells</cell_type> .


This was identified as the mRNA encoding the transcription factor egr-1 , which is expressed with fast kinetics in T and NK cells upon IL-2 , but not IL-12 , stimulation .

This was identified as the <rna>mRNA</rna> encoding the <protein>transcription factor</protein> <protein>egr-1</protein> , which is expressed with fast kinetics in <cell_type>T and NK cells</cell_type> upon <protein>IL-2</protein> , but not <protein>IL-12</protein> , stimulation .


Analysis of the accumulation of mRNA-encoding members of the AP-1 transcription factor family demonstrated that c-fos and junB are also expressed upon stimulation of NK and T cells with IL-2 , but not IL-12 , whereas expression of c-jun and junD is not modified by either cytokine .

Analysis of the accumulation of <protein>mRNA-encoding members</protein> of the <protein>AP-1 transcription factor family</protein> demonstrated that <dna>c-fos</dna> and <dna>junB</dna> are also expressed upon stimulation of <cell_type>NK and T cells</cell_type> with <protein>IL-2</protein> , but not <protein>IL-12</protein> , whereas expression of <dna>c-jun</dna> and <dna>junD</dna> is not modified by either <protein>cytokine</protein> .


Accordingly , increased AP-1 DNA-binding activity and AP-1 -dependent transcriptional activity were detected exclusively in IL-2-stimulated cells .

Accordingly , increased <protein>AP-1</protein> DNA-binding activity and <protein>AP-1</protein> -dependent transcriptional activity were detected exclusively in <cell_line>IL-2-stimulated cells</cell_line> .


Analysis of the expression of genes reported to regulate cytokine -induced proliferation demonstrated that both IL-2 and IL-12 induce c-myc mRNA accumulation in NK and T cells , whereas only IL-2 induces bcl-2 expression .

Analysis of the expression of <protein>genes</protein> reported to regulate <protein>cytokine</protein> -induced proliferation demonstrated that both <protein>IL-2</protein> and <protein>IL-12</protein> induce <rna>c-myc mRNA</rna> accumulation in <cell_type>NK and T cells</cell_type> , whereas only <protein>IL-2</protein> induces <dna>bcl-2</dna> expression .


Our data provide the first demonstration that IL-12 -mediated activation of T and NK cells does not involve expression of members of the immediate-early activation genes family ( egr-1 , c-fos , and junB ) , AP-1 transcriptional activity , or bcl-2 expression .

Our data provide the first demonstration that <protein>IL-12</protein> -mediated activation of <cell_type>T and NK cells</cell_type> does not involve expression of members of the <dna>immediate-early activation genes family</dna> ( <dna>egr-1</dna> , <dna>c-fos</dna> , and <dna>junB</dna> ) , <protein>AP-1</protein> transcriptional activity , or <dna>bcl-2</dna> expression .


This indicates that functional differences observed in IL-2- and IL-12-stimulated cells may depend , at least in part , on differential gene regulation .

This indicates that functional differences observed in <cell_line>IL-2- and IL-12-stimulated cells</cell_line> may depend , at least in part , on differential gene regulation .


Active suppression of the class II transactivator-encoding AIR-1 locus is responsible for the lack of major histocompatibility complex class II gene expression observed during differentiation from B cells to plasma cells .

Active suppression of the <dna>class II transactivator-encoding AIR-1 locus</dna> is responsible for the lack of <dna>major histocompatibility complex class II gene</dna> expression observed during differentiation from <cell_type>B cells</cell_type> to <cell_type>plasma cells</cell_type> .


In this study the genetic control of major histocompatibility complex ( MHC ) class II gene expression during the transition from B cell to plasma cell has been analyzed .

In this study the genetic control of <dna>major histocompatibility complex ( MHC ) class II gene</dna> expression during the transition from <cell_type>B cell</cell_type> to <cell_type>plasma cell</cell_type> has been analyzed .


Class II molecules are not expressed in plasma cells because of an active suppression resulting in the abrogation of class II gene transcription .

<protein>Class II molecules</protein> are not expressed in <cell_type>plasma cells</cell_type> because of an active suppression resulting in the abrogation of <dna>class II gene</dna> transcription .


We show here that the plasma cell-specific repressor function , designated SIR ( suppressor of immune response genes ) , does not act directly on the transcription of class II genes , but instead on the transcription of the AIR-1 gene , whose product , the class II transactivator ( CIITA ) , is fundamental for the regulation of the constitutive and inducible expression of MHC class II genes .

We show here that the plasma cell-specific repressor function , designated <dna>SIR</dna> ( <dna>suppressor of immune response genes</dna> ) , does not act directly on the transcription of <dna>class II genes</dna> , but instead on the transcription of the <dna>AIR-1 gene</dna> , whose product , the <protein>class II transactivator</protein> ( <protein>CIITA</protein> ) , is fundamental for the regulation of the constitutive and inducible expression of <dna>MHC class II genes</dna> .


This was unambiguously demonstrated by the fact that plasmacytoma x B cell hybrids carrying an AIR-1 locus derived from CIITA-expressing cells do not express CIITA-specific transcripts .

This was unambiguously demonstrated by the fact that <cell_line>plasmacytoma x B cell hybrids</cell_line> carrying an <dna>AIR-1 locus</dna> derived from <cell_line>CIITA-expressing cells</cell_line> do not express <rna>CIITA-specific transcripts</rna> .


Transfection of a cDNA containing the human CIITA coding sequence under the control of an heterologous promoter restores expression of human MHC class II genes in the hybrids and is responsible for de novo expression of mouse MHC class II genes in both the mouse plasmacytoma cell line and the hybrids .

Transfection of a cDNA containing the <dna>human CIITA coding sequence</dna> under the control of an <dna>heterologous promoter</dna> restores expression of <dna>human MHC class II genes</dna> in the hybrids and is responsible for de novo expression of <dna>mouse MHC class II genes</dna> in both the <cell_line>mouse plasmacytoma cell line</cell_line> and the <cell_line>hybrids</cell_line> .


These results confirm and extend the notion of the functional conservation of the AIR-1 gene product across species barriers .

These results confirm and extend the notion of the functional conservation of the <protein>AIR-1 gene product</protein> across species barriers .


Interestingly , in CIITA-transfected cell hybrids , cell surface expression of the human HLA-DQ heterodimer was not observed .

Interestingly , in <cell_line>CIITA-transfected cell hybrids</cell_line> , cell surface expression of the <protein>human HLA-DQ heterodimer</protein> was not observed .


This result was not attributable to lack of HLA-DQ alpha or -DQ beta transcription , because both transcripts were present in the CIITA-transfected hybrids , although at reduced levels .

This result was not attributable to lack of HLA-DQ alpha or -DQ beta transcription , because both transcripts were present in the <cell_line>CIITA-transfected hybrids</cell_line> , although at reduced levels .


These findings further support our previous observations on the distinct regulation of expression of the human HLA-DQ class II subset , which may be thus controlled at the posttranscriptional level by a CIITA -independent mechanism .

These findings further support our previous observations on the distinct regulation of expression of the <dna>human HLA-DQ class II subset</dna> , which may be thus controlled at the posttranscriptional level by a <protein>CIITA</protein> -independent mechanism .


Requirements for induction of vitamin D-mediated gene regulation in normal human B lymphocytes .

Requirements for induction of vitamin D-mediated gene regulation in <cell_type>normal human B lymphocytes</cell_type> .


Mature human lymphocytes are unique targets of 1 alpha , 25-dihydroxyvitamin D3 ( 1 alpha , 25 ( OH ) 2D3 ) in that vitamin D receptors ( VDR ) are not constitutively expressed , and specific cellular activation signals are required for both the up-regulation of VDR and establishment of reactivity to the lipophilic ligand .

Mature <cell_type>human lymphocytes</cell_type> are unique targets of 1 alpha , 25-dihydroxyvitamin D3 ( 1 alpha , 25 ( OH ) 2D3 ) in that <protein>vitamin D receptors</protein> ( <protein>VDR</protein> ) are not constitutively expressed , and specific cellular activation signals are required for both the up-regulation of <protein>VDR</protein> and establishment of reactivity to the lipophilic ligand .


Treatment of B lymphocytes with the cytokine IL-4 ( IL-4 ) , in the absence of prior activation , induces a weak up-regulation of VDR expression but fails to generate vitamin D-responsive element ( VDRE ) -reactive nuclear protein complexes or to initiate the genomic transcription of 25-hydroxyvitamin D3 24-hydroxylase .

Treatment of <cell_type>B lymphocytes</cell_type> with the <protein>cytokine</protein> <protein>IL-4</protein> ( <protein>IL-4</protein> ) , in the absence of prior activation , induces a weak up-regulation of <protein>VDR</protein> expression but fails to generate <protein>vitamin D-responsive element ( VDRE ) -reactive nuclear protein complexes</protein> or to initiate the genomic transcription of <protein>25-hydroxyvitamin D3 24-hydroxylase</protein> .


Stimulation of B lymphocytes by either ligation of CD40 Ag or cross-linking the Ig receptor is also insufficient to render B lymphocytes responsive to 1 alpha , 25 ( OH ) 2D3 .

Stimulation of <cell_type>B lymphocytes</cell_type> by either ligation of <protein>CD40 Ag</protein> or cross-linking the <protein>Ig receptor</protein> is also insufficient to render <cell_type>B lymphocytes</cell_type> responsive to 1 alpha , 25 ( OH ) 2D3 .


However , this apparent lack of response to the secosterol can be overcome by stimulation of B lymphocytes with a combination of these cellular activation signals , which are sufficient to lead to G1 cell cycle progression .

However , this apparent lack of response to the secosterol can be overcome by stimulation of <cell_type>B lymphocytes</cell_type> with a combination of these cellular activation signals , which are sufficient to lead to G1 cell cycle progression .


In the presence of 1 alpha , 25 ( OH ) 2D3 , cellular activation associated with stimulation of such a progression appears to be sufficient for the up-regulation of VDR message and protein and necessary for the establishment of VDRE binding complexes and the induction of 24-hydroxylase message .

In the presence of 1 alpha , 25 ( OH ) 2D3 , cellular activation associated with stimulation of such a progression appears to be sufficient for the up-regulation of <protein>VDR</protein> message and protein and necessary for the establishment of <protein>VDRE binding complexes</protein> and the induction of <protein>24-hydroxylase</protein> message .


Furthermore , biologic functions are modulated , in that the hormone inhibits proliferation in a subset of the activated B cells .

Furthermore , biologic functions are modulated , in that the hormone inhibits proliferation in a subset of the activated <cell_type>B cells</cell_type> .


These observations suggest that reactivity to 1 alpha , 25 ( OH ) 2D3 is tightly regulated in B lymphocytes , requiring specific signals for its initiation .

These observations suggest that reactivity to 1 alpha , 25 ( OH ) 2D3 is tightly regulated in <cell_type>B lymphocytes</cell_type> , requiring specific signals for its initiation .


Cross talk between cell death and cell cycle progression : BCL-2 regulates NFAT -mediated activation .

Cross talk between cell death and cell cycle progression : <protein>BCL-2</protein> regulates <protein>NFAT</protein> -mediated activation .


BCL-2-deficient T cells demonstrate accelerated cell cycle progression and increased apoptosis following activation .

<cell_line>BCL-2-deficient T cells</cell_line> demonstrate accelerated cell cycle progression and increased apoptosis following activation .


Increasing the levels of BCL-2 retarded the G0 -- > S transition , sustained the levels of cyclin-dependent kinase inhibitor p27Kip1 , and repressed postactivation death .

Increasing the levels of <protein>BCL-2</protein> retarded the G0 -- > S transition , sustained the levels of <protein>cyclin-dependent kinase</protein> inhibitor p27Kip1 , and repressed postactivation death .


Proximal signal transduction events and immediate early gene transcription were unaffected .

Proximal signal transduction events and <dna>immediate early gene</dna> transcription were unaffected .


However , the transcription and synthesis of interleukin 2 and other delayed early cytokines were markedly attenuated by BCL-2 .

However , the transcription and synthesis of <protein>interleukin 2</protein> and other delayed early <protein>cytokines</protein> were markedly attenuated by <protein>BCL-2</protein> .


In contrast , a cysteine protease inhibitor that also blocks apoptosis had no substantial affect upon cytokine production .

In contrast , a cysteine protease inhibitor that also blocks apoptosis had no substantial affect upon <protein>cytokine</protein> production .


InterleUkin 2 expression requires several transcription factors of which nuclear translocation of NFAT ( nuclear factor of activated T cells ) and NFAT -mediated transactivation were impaired by BCL-2 .

<protein>InterleUkin 2</protein> expression requires several <protein>transcription factors</protein> of which nuclear translocation of <protein>NFAT</protein> ( <protein>nuclear factor of activated T cells</protein> ) and <protein>NFAT</protein> -mediated transactivation were impaired by <protein>BCL-2</protein> .


Thus , select genetic aberrations in the apoptotic pathway reveal a cell autonomous coregulation of activation .


Interaction of the human T-cell lymphotropic virus type 1 tax transactivator with transcription factor IIA .

Interaction of the <protein>human T-cell lymphotropic virus type 1 tax transactivator</protein> with <protein>transcription factor IIA</protein> .


The Tax protein of human T-cell lymphotropic virus type 1 ( HTLV-1 ) is a 40-kDa transcriptional activator which is critical for HTLV-1 gene regulation and virus-induced cellular transformation .

The <protein>Tax protein</protein> of human T-cell lymphotropic virus type 1 ( HTLV-1 ) is a <protein>40-kDa transcriptional activator</protein> which is critical for HTLV-1 gene regulation and virus-induced cellular transformation .


Tax is localized to the DNA through its interaction with the site-specific activators cyclic AMP-responsive element-binding protein , NF-kappaB , and serum response factor .

<protein>Tax</protein> is localized to the DNA through its interaction with the <protein>site-specific activators</protein> <protein>cyclic AMP-responsive element-binding protein</protein> , <protein>NF-kappaB</protein> , and <protein>serum response factor</protein> .


It has been suggested that the recruitment of Tax to the DNA positions Tax for interaction with the basal transcriptional machinery .

It has been suggested that the recruitment of <protein>Tax</protein> to the DNA positions <protein>Tax</protein> for interaction with the basal transcriptional machinery .


On the basis of several independent assays , we now report a physical and functional interaction between Tax and the transcription factor , TFIIA .

On the basis of several independent assays , we now report a physical and functional interaction between <protein>Tax</protein> and the <protein>transcription factor</protein> , <protein>TFIIA</protein> .


First , Tax was found to interact with the 35-kDa ( alpha ) subunit of TFIIA in the yeast two-hybrid interaction system .

First , <protein>Tax</protein> was found to interact with the <protein>35-kDa ( alpha ) subunit</protein> of <protein>TFIIA</protein> in the yeast two-hybrid interaction system .


Importantly , two previously characterized mutants with point mutations in Tax , M32 ( Y196A , K197S ) and M41 ( H287A , P288S ) , which were shown to be defective in Tax -activated transcription were unable to interact with TFIIA in this assay .

Importantly , two previously characterized <protein>mutants</protein> with point mutations in <protein>Tax</protein> , <protein>M32</protein> ( Y196A , K197S ) and <protein>M41</protein> ( H287A , P288S ) , which were shown to be defective in <protein>Tax</protein> -activated transcription were unable to interact with <protein>TFIIA</protein> in this assay .


Second , a glutathione-S-transferase ( GST ) affinity-binding assay showed that the interaction of holo- TFIIA with GST-Tax was 20-fold higher than that observed with either the GST-Tax M32 activation mutant or the GST control .

Second , a glutathione-S-transferase ( <protein>GST</protein> ) affinity-binding assay showed that the interaction of holo- <protein>TFIIA</protein> with <protein>GST-Tax</protein> was 20-fold higher than that observed with either the <protein>GST-Tax M32 activation mutant</protein> or the GST control .


Third , a coimmunoprecipitation assay showed that in HTLV-1-infected human T lymphocytes , Tax and TFIIA were associated .

Third , a coimmunoprecipitation assay showed that in <cell_line>HTLV-1-infected human T lymphocytes</cell_line> , <protein>Tax</protein> and <protein>TFIIA</protein> were associated .


Finally , TFIIA facilitates Tax transactivation in vitro and in vivo .

Finally , <protein>TFIIA</protein> facilitates <protein>Tax</protein> transactivation in vitro and in vivo .


In vitro transcription studies showed reduced levels of Tax -activated transcription in cell extracts depleted of TFIIA .

In vitro transcription studies showed reduced levels of <protein>Tax</protein> -activated transcription in cell extracts depleted of <protein>TFIIA</protein> .


In addition , transfection of human T lymphocytes with TFIIA expression vectors enhanced Tax -activated transcription of an HTLV-1 long terminal repeat-chloramphenicol acetyltransferase reporter construct .

In addition , transfection of <cell_type>human T lymphocytes</cell_type> with <dna>TFIIA expression vectors</dna> enhanced <protein>Tax</protein> -activated transcription of an <dna>HTLV-1 long terminal repeat-chloramphenicol acetyltransferase reporter construct</dna> .


Our study suggests that the interaction of Tax with the transcription factor TFIIA may play a role in Tax -mediated transcriptional activation .

Our study suggests that the interaction of <protein>Tax</protein> with the <protein>transcription factor</protein> <protein>TFIIA</protein> may play a role in <protein>Tax</protein> -mediated transcriptional activation .


Inhibition of transcription factor Stat1 activity in mononuclear cell cultures and T cells by the cyclic AMP signaling pathway .

Inhibition of <protein>transcription factor</protein> <protein>Stat1</protein> activity in <cell_line>mononuclear cell cultures</cell_line> and <cell_type>T cells</cell_type> by the cyclic AMP signaling pathway .


Activation of T cells results in a cascade of gene activation and subsequent proliferation and differentiation into effector phenotypes .

Activation of <cell_type>T cells</cell_type> results in a cascade of gene activation and subsequent proliferation and differentiation into effector phenotypes .


The regulation of transcription factors belonging to the signal transducer and activator of transcription ( STAT ) family was analyzed in PHA-activated mononuclear cells and in purified T cells activated by cross-linking cell surface CD3 .

The regulation of <protein>transcription factors</protein> belonging to the <protein>signal transducer and activator of transcription ( STAT ) family</protein> was analyzed in <cell_line>PHA-activated mononuclear cells</cell_line> and in <cell_line>purified T cells</cell_line> activated by cross-linking <protein>cell surface CD3</protein> .


Cell activation resulted in a delayed induction of STAT DNA-binding activity , which was sustained for several days , was composed predominantly of Stat1 and Stat3 , and was blocked by cycloheximide and actinomycin D .

Cell activation resulted in a delayed induction of <protein>STAT</protein> DNA-binding activity , which was sustained for several days , was composed predominantly of <protein>Stat1</protein> and <protein>Stat3</protein> , and was blocked by cycloheximide and actinomycin D .


Increased Stat1 and Stat3 mRNA and protein levels were detected , respectively 4 and 24 h after activation .


Stimulation of the cAMP signal transduction pathway , which skews cytokine production toward a Th2 pattern , resulted in the preferential suppression of Stat1 activity .

Stimulation of the cAMP signal transduction pathway , which skews <protein>cytokine</protein> production toward a Th2 pattern , resulted in the preferential suppression of <protein>Stat1</protein> activity .


cAMP inhibited the induction of expression of IL-2 receptor components , but did not inhibit IL-4 receptor alpha-chain and CD69 expression or the induction of activator protein 1 transcription factors .

cAMP inhibited the induction of expression of <protein>IL-2 receptor components</protein> , but did not inhibit <protein>IL-4 receptor alpha-chain</protein> and <protein>CD69</protein> expression or the induction of <protein>activator protein 1 transcription factors</protein> .


cAMP signaling inhibited Stat1 at several different levels , including suppression of DNA binding and down-regulation of Stat1 protein and mRNA levels .

cAMP signaling inhibited <protein>Stat1</protein> at several different levels , including suppression of DNA binding and down-regulation of Stat1 protein and mRNA levels .


Our results demonstrate the regulation of STAT activity by a signaling pathway that regulates the T cell functional phenotype and is distinct from the cytokine -activated Janus kinase -STAT signaling pathway .

Our results demonstrate the regulation of <protein>STAT</protein> activity by a signaling pathway that regulates the T cell functional phenotype and is distinct from the <protein>cytokine</protein> -activated <protein>Janus kinase</protein> <protein>-STAT</protein> signaling pathway .


Suppression of c-jun by antisense oligonucleotides inhibits cell adhesion but not respiratory burst during phorbol ester-induced differentiation of U937 human monoblastic cells .

Suppression of <dna>c-jun</dna> by antisense oligonucleotides inhibits cell adhesion but not respiratory burst during phorbol ester-induced differentiation of <cell_line>U937 human monoblastic cells</cell_line> .


We studied the role of the immediate early gene c-jun in cell proliferation and phorbol 12-myristate 13-acetate ( PMA ) -induced differentiation in U937 human monoblastic cells , using c-jun -specific antisense ( AS ) phosphorothioate oligonucleotides .

We studied the role of the <dna>immediate early gene</dna> <dna>c-jun</dna> in cell proliferation and phorbol 12-myristate 13-acetate ( PMA ) -induced differentiation in <cell_line>U937 human monoblastic cells</cell_line> , using <dna>c-jun</dna> -specific antisense ( AS ) phosphorothioate oligonucleotides .


In selecting the most specific and potent oligonucleotide sequence , we performed extensive analyses for the binding specificity between all candidates of c-jun AS oligonucleotides and the whole sequences in GenBank database , using a computer program .

In selecting the most specific and potent oligonucleotide sequence , we performed extensive analyses for the binding specificity between all candidates of <dna>c-jun</dna> AS oligonucleotides and the whole sequences in GenBank database , using a computer program .


Among the 20 selected oligonucleotides , two potent 15-mer AS oligonucleotides ( C-JUN AS oligonucleotides ) exhibited significant inhibition of cell growth in a dose-dependent manner between 2 and 10 microM .


Reverse transcription-PCR and Western blot analysis demonstrated that 10 microM of C-JUN AS oligonucleotides reduced c-jun expression at both the mRNA and protein levels .

Reverse transcription-PCR and Western blot analysis demonstrated that 10 microM of C-JUN AS oligonucleotides reduced <dna>c-jun</dna> expression at both the <rna>mRNA</rna> and protein levels .


More importantly , C-JUN AS oligonucleotides showed distinct effects on two markers of PMA-induced differentiation ; the C-JUN AS oligonucleotides inhibited cell adhesion , whereas they did not affect another marker of differentiation , respiratory burst ( measured by nitro blue tetrazolium reduction assay ) .


These results suggest a critical role of c-jun in both cell proliferation and PMA-induced cell adhesion but not in PMA-induced respiratory burst in U937 cells .

These results suggest a critical role of <dna>c-jun</dna> in both cell proliferation and PMA-induced cell adhesion but not in PMA-induced respiratory burst in <cell_line>U937 cells</cell_line> .


Effects of IL-10 and IL-4 on LPS-induced transcription factors ( AP-1 , NF-IL6 and NF-kappa B ) which are involved in IL-6 regulation .

Effects of <protein>IL-10</protein> and <protein>IL-4</protein> on LPS-induced <protein>transcription factors</protein> ( <protein>AP-1</protein> , <protein>NF-IL6</protein> and <protein>NF-kappa B</protein> ) which are involved in <protein>IL-6</protein> regulation .


Interleukin-10 ( IL-10 ) , like IL-4 , is known to inhibit cytokine expression in activated human monocytes .

<protein>Interleukin-10</protein> ( <protein>IL-10</protein> ) , like <protein>IL-4</protein> , is known to inhibit <protein>cytokine</protein> expression in <cell_type>activated human monocytes</cell_type> .


We showed that both IL-10 and IL-4 inhibit LPS-induced IL-6 mRNA and protein expression by inhibiting the transcription rate of the IL-6 gene .

We showed that both <protein>IL-10</protein> and <protein>IL-4</protein> inhibit <rna>LPS-induced IL-6 mRNA</rna> and protein expression by inhibiting the transcription rate of the <dna>IL-6 gene</dna> .


The strong inhibition of the IL-6 transcription rate prompted us to study the effect of IL-10 and IL-4 on the expression of transcription factors .

The strong inhibition of the <protein>IL-6</protein> transcription rate prompted us to study the effect of <protein>IL-10</protein> and <protein>IL-4</protein> on the expression of <protein>transcription factors</protein> .


We questioned whether or not IL-10 and IL-4 affected the expression of transcription factors that are known to be involved in the control of the IL-6 transcription rate , namely activator protein-1 ( AP-1 ) , nuclear factor IL-6 ( NF-IL6 ) , and nuclear factor kappa B ( NF-kappaB ) .

We questioned whether or not <protein>IL-10</protein> and <protein>IL-4</protein> affected the expression of <protein>transcription factors</protein> that are known to be involved in the control of the <protein>IL-6</protein> transcription rate , namely activator protein-1 ( <protein>AP-1</protein> ) , <protein>nuclear factor</protein> <protein>IL-6</protein> ( <protein>NF-IL6</protein> ) , and <protein>nuclear factor kappa B</protein> ( <protein>NF-kappaB</protein> ) .


In electrophoretic mobility shift assays ( EMSAs ) we showed that IL-10 and IL-4 inhibited LPS-induced AP-1 binding activity .

In electrophoretic mobility shift assays ( EMSAs ) we showed that <protein>IL-10</protein> and <protein>IL-4</protein> inhibited LPS-induced <protein>AP-1</protein> binding activity .


The inhibiting effect of IL-4 was slightly more pronounced than that of IL-10 .

The inhibiting effect of <protein>IL-4</protein> was slightly more pronounced than that of <protein>IL-10</protein> .


Downregulation of LPS-induced AP-1 was accompanied , and thus possibly explained , by a reduced expression at mRNA level of the two major components of the AP-1 complex , namely c-fos and c-jun as determined by Northern experiments .

Downregulation of <protein>LPS-induced AP-1</protein> was accompanied , and thus possibly explained , by a reduced expression at <rna>mRNA</rna> level of the two major components of the <protein>AP-1 complex</protein> , namely <dna>c-fos</dna> and <dna>c-jun</dna> as determined by Northern experiments .


Binding activity of NF-IL6 was also strongly inhibited by IL-4 whereas IL-10 showed no effect .

Binding activity of <protein>NF-IL6</protein> was also strongly inhibited by <protein>IL-4</protein> whereas <protein>IL-10</protein> showed no effect .


NF-IL6 mRNA levels were not affected by IL-10 or IL-4 , suggesting that IL-4 affects binding activity of preexisting NF-IL6 .

<rna>NF-IL6 mRNA</rna> levels were not affected by <protein>IL-10</protein> or <protein>IL-4</protein> , suggesting that <protein>IL-4</protein> affects binding activity of preexisting <protein>NF-IL6</protein> .


Neither IL-10 nor IL-4 inhibited LPS-induced NF-kappa B binding activity .

Neither <protein>IL-10</protein> nor <protein>IL-4</protein> inhibited LPS-induced <protein>NF-kappa B</protein> binding activity .


In agreement with this finding , Northern experiments where p65 and p105 mRNA levels were determined , demonstrated that expression of these components of the NF-kappa B transcription factor were not affected by IL-10 or IL-4 .

In agreement with this finding , Northern experiments where p65 and p105 mRNA levels were determined , demonstrated that expression of these components of the <protein>NF-kappa B</protein> transcription factor were not affected by <protein>IL-10</protein> or <protein>IL-4</protein> .


Furthermore , neither IL-10 nor IL-4 showed any effect on I-kappa B mRNA expression as determined by Northern experiments .

Furthermore , neither <protein>IL-10</protein> nor <protein>IL-4</protein> showed any effect on <rna>I-kappa B mRNA</rna> expression as determined by Northern experiments .


Thus , IL-10 and IL-4 similarly affect IL-6 expression .

Thus , <protein>IL-10</protein> and <protein>IL-4</protein> similarly affect <protein>IL-6</protein> expression .


However , for IL-4 this was accompanied with a reduction of AP-1 and NF-IL6 binding activity whereas IL-10 only inhibited AP-1 binding activity .

However , for <protein>IL-4</protein> this was accompanied with a reduction of AP-1 and NF-IL6 binding activity whereas <protein>IL-10</protein> only inhibited <protein>AP-1</protein> binding activity .


Regulation of GM-CSF gene transcription by core-binding factor .

Regulation of <dna>GM-CSF gene</dna> transcription by <protein>core-binding factor</protein> .


GM-CSF gene activation in T cells is known to involve the transcription factors nuclear factor-kappa B , AP-1 , NFAT , and Sp1 .

<dna>GM-CSF gene</dna> activation in <cell_type>T cells</cell_type> is known to involve the <protein>transcription factors</protein> <protein>nuclear factor-kappa B</protein> , <protein>AP-1</protein> , <protein>NFAT</protein> , and Sp1 .


Here we demonstrate that the human GM-CSF promoter and enhancer also encompass binding sites for core-binding factor ( CBF ) .

Here we demonstrate that the <dna>human GM-CSF promoter and enhancer</dna> also encompass binding sites for <protein>core-binding factor</protein> ( <protein>CBF</protein> ) .


Significantly , the CBF sites are in each case contained within the minimum essential core regions required for inducible activation of transcription .

Significantly , the <dna>CBF sites</dna> are in each case contained within the minimum <dna>essential core regions</dna> required for inducible activation of transcription .


Furthermore , these core regions of the enhancer and promoter each encompass closely linked binding sites for CBF , AP-1 , and NFATp .

Furthermore , these core regions of the enhancer and promoter each encompass <dna>closely linked binding sites</dna> for <protein>CBF</protein> , <protein>AP-1</protein> , and <protein>NFATp</protein> .


The GM-CSF promoter CBF site TGTGGTCA is located 51 bp upstream of the transcription start site and also overlaps a YY-1 binding site .

The <dna>GM-CSF promoter CBF site</dna> TGTGGTCA is located <dna>51 bp upstream</dna> of the <dna>transcription start site</dna> and also overlaps a <dna>YY-1 binding site</dna> .


A 2-bp mutation within the CBF site resulted in a 2-3-fold decrease in the activities of both a 69-bp proximal promoter fragment and a 627-bp full-length promoter fragment .

A <dna>2-bp mutation</dna> within the <protein>CBF</protein> site resulted in a 2-3-fold decrease in the activities of both a <dna>69-bp proximal promoter fragment</dna> and a <dna>627-bp full-length promoter fragment</dna> .


Stepwise deletions into the proximal promoter also revealed that the CBF site , but not the YY-1 site , was required for efficient induction of transcriptional activation .

Stepwise deletions into the <dna>proximal promoter</dna> also revealed that the <protein>CBF</protein> site , but not the <dna>YY-1 site</dna> , was required for efficient induction of transcriptional activation .


The AML1 and CBF beta genes that encode CBF each have the ability to influence cell growth and differentiation and have been implicated as proto-oncogenes in acute myeloid leukemia .

The <dna>AML1 and CBF beta genes</dna> that encode <protein>CBF</protein> each have the ability to influence cell growth and differentiation and have been implicated as <dna>proto-oncogenes</dna> in acute myeloid leukemia .


This study adds GM-CSF to a growing list of cytokines and receptors that are regulated by CBF and which control the growth , differentiation , and activation of hemopoietic cells .

This study adds <protein>GM-CSF</protein> to a growing list of <protein>cytokines</protein> and receptors that are regulated by <protein>CBF</protein> and which control the growth , differentiation , and activation of <cell_type>hemopoietic cells</cell_type> .


The GM-CSF locus may represent one of several target genes that are dysregulated in acute myeloid leukemia .

The <dna>GM-CSF locus</dna> may represent one of several target <protein>genes</protein> that are dysregulated in acute myeloid leukemia .


Sublethal levels of oxidative stress stimulate transcriptional activation of c-jun and suppress IL-2 promoter activation in Jurkat T cells .

Sublethal levels of oxidative stress stimulate transcriptional activation of <dna>c-jun</dna> and suppress <dna>IL-2 promoter</dna> activation in <cell_line>Jurkat T cells</cell_line> .


Sublethal levels of oxidative stress are well known to alter T cell functional responses , but the underlying mechanisms are unknown .


The current study examined the effects of oxidative stress on transcriptional activities mediated by c-Fos/c-Jun AP-1 and the nuclear factor of activated T cells ( NF-AT ) .

The current study examined the effects of oxidative stress on transcriptional activities mediated by <protein>c-Fos/c-Jun</protein> <protein>AP-1</protein> and the <protein>nuclear factor of activated T cells</protein> ( <protein>NF-AT</protein> ) .


The present results show that Jurkat T cells acutely exposed to micromolar concentrations of H2O2 exhibit substantial increases in AP-1 binding activity and the expression of c-jun but not c-fos mRNA .

The present results show that <cell_line>Jurkat T cells</cell_line> acutely exposed to micromolar concentrations of H2O2 exhibit substantial increases in <protein>AP-1</protein> binding activity and the expression of <dna>c-jun</dna> but not <rna>c-fos mRNA</rna> .


The preferential induction of c-jun by H2O2 did not represent redox stabilization of mRNA transcripts , and oxidative signals closely resembled PHA/PMA stimulation by effectively transactivating the full length c-jun promoter via the proximal jun1 tumor promoter-responsive element ( TRE ) -like promoter element .

The preferential induction of <dna>c-jun</dna> by H2O2 did not represent redox stabilization of <rna>mRNA transcripts</rna> , and oxidative signals closely resembled PHA/PMA stimulation by effectively transactivating the full length <dna>c-jun</dna> promoter via the <dna>proximal jun1 tumor promoter-responsive element ( TRE ) -like promoter element</dna> .


Similarly , the complexes binding the consensus AP-1 TRE and jun TRE-like motifs in cells exposed to oxidative signals or PHA/PMA were indistinguishable , being composed of c-Fos , c-Jun , and JunD .

Similarly , the complexes binding the <dna>consensus AP-1 TRE</dna> and <dna>jun TRE-like motifs</dna> in cells exposed to oxidative signals or PHA/PMA were indistinguishable , being composed of <protein>c-Fos</protein> , <protein>c-Jun</protein> , and <protein>JunD</protein> .


However , PHA/PMA but not oxidative signals induced the coordinate activation of reporter constructs containing the AP-1-TRE , NF-AT , and IL-2 promoter regions along with IL-2 mRNA expression .

However , PHA/PMA but not oxidative signals induced the coordinate activation of <dna>reporter constructs</dna> containing the <dna>AP-1-TRE , NF-AT , and IL-2 promoter regions</dna> along with <rna>IL-2 mRNA</rna> expression .


Furthermore , sublethal levels of H2O2 actively suppressed the transcriptional activation of NF-AT and IL-2 reporters as well as the expression of IL-2 mRNA in cells stimulated with PHA/PMA .

Furthermore , sublethal levels of H2O2 actively suppressed the transcriptional activation of <protein>NF-AT</protein> and <dna>IL-2 reporters</dna> as well as the expression of <rna>IL-2 mRNA</rna> in cells stimulated with PHA/PMA .


Gel shift analysis revealed that oxidative suppression of NF-AT represented inhibition in the early generation of NFAT complexes rather than the binding of preformed NF-AT complexes .

Gel shift analysis revealed that oxidative suppression of <protein>NF-AT</protein> represented inhibition in the early generation of <protein>NFAT complexes</protein> rather than the binding of preformed <protein>NF-AT complexes</protein> .


These results suggest that oxidative signals can positively and negatively regulate T cell transcriptional events and that changes in cellular redox can uncouple AP-1 regulation of c-jun from transcriptional up-regulation of IL-2 via NF-AT .

These results suggest that oxidative signals can positively and negatively regulate <cell_type>T cell</cell_type> transcriptional events and that changes in cellular redox can uncouple <protein>AP-1</protein> regulation of <dna>c-jun</dna> from transcriptional up-regulation of <protein>IL-2</protein> via <protein>NF-AT</protein> .


Inorganic lead activates NF-kappa B in primary human CD4+ T lymphocytes .

Inorganic lead activates <protein>NF-kappa B</protein> in <cell_type>primary human CD4+ T lymphocytes</cell_type> .


Inorganic lead ( Pb ) is a ubiquitous environmental contaminant that produces a variety of effects on humoral and cell mediated immune responses .


The underlying molecular mechanism for Pb 's complex effects on the immune system remain obscure .


Many of Pb 's effects on the immune system could be explained through activation of the transcription factor , NF-kappa B .

Many of Pb 's effects on the immune system could be explained through activation of the <protein>transcription factor</protein> , <protein>NF-kappa B</protein> .


NF-kappa B is critical for T lymphocyte function and is a strong inducer of HIV-LTR activation .

<protein>NF-kappa B</protein> is critical for T lymphocyte function and is a strong inducer of <dna>HIV-LTR</dna> activation .


We demonstrate that Pb at physiologically relevant concentrations activates NF-kappa B in primary human CD4+ T lymphocytes .

We demonstrate that Pb at physiologically relevant concentrations activates <protein>NF-kappa B</protein> in <cell_type>primary human CD4+ T lymphocytes</cell_type> .


Pb-induced activation of NF-kappa B is blocked by antibodies for p65 and p50 subunits but not cRel , indicating that the p65 : p50 heterodimer ( NF-kappa B ) is involved .

Pb-induced activation of <protein>NF-kappa B</protein> is blocked by <protein>antibodies</protein> for <protein>p65</protein> and <protein>p50</protein> subunits but not <protein>cRel</protein> , indicating that the <protein>p65 : p50 heterodimer</protein> ( <protein>NF-kappa B</protein> ) is involved .


Functional activation of gene expression by Pb was confirmed using primary CD4+ T cells transfected with an NF-kappa B dependent reporter gene construct .

Functional activation of gene expression by Pb was confirmed using <cell_line>primary CD4+ T cells</cell_line> transfected with an <dna>NF-kappa B dependent reporter gene construct</dna> .


Pb did not activate NF-kappa B in 4 different T cell lines , suggesting that lymphoid cell lines may not be reliable surrogates for the study of transcriptional activation in human T cells .

Pb did not activate <protein>NF-kappa B</protein> in 4 different <cell_line>T cell lines</cell_line> , suggesting that lymphoid cell lines may not be reliable surrogates for the study of transcriptional activation in <cell_type>human T cells</cell_type> .


These data suggest that NF-kappa B may be an important molecular mediator of Pb-induced immunotoxicity .

These data suggest that <protein>NF-kappa B</protein> may be an important molecular mediator of Pb-induced immunotoxicity .


Tyrosine kinase and cAMP-dependent protein kinase activities in CD40-activated human B lymphocytes .

<protein>Tyrosine kinase</protein> and <protein>cAMP-dependent protein kinase</protein> activities in <cell_line>CD40-activated human B lymphocytes</cell_line> .


In vitro , human B lymphocytes undergo long-term proliferation when activated through CD40 , a protein expressed on their cell surface .

In vitro , <cell_type>human B lymphocytes</cell_type> undergo long-term proliferation when activated through <protein>CD40</protein> , a protein expressed on their cell surface .


The nature of CD40 -dependent signals in proliferating fresh human Epstein-Barr virus-negative B lymphocytes is currently unknown .

The nature of <protein>CD40</protein> -dependent signals in proliferating fresh <cell_line>human Epstein-Barr virus-negative B lymphocytes</cell_line> is currently unknown .


In this study , a CD40 -dependent B cell culture system was used to examine the role of different signal transduction elements .

In this study , a <protein>CD40</protein> -dependent B cell culture system was used to examine the role of different <dna>signal transduction elements</dna> .


Protein kinase C ( PKC ) depletion generated by a long-term phorbol 12 myristate 13-acetate treatment had weak effects on proliferation .

Protein kinase C ( <protein>PKC</protein> ) depletion generated by a long-term phorbol 12 myristate 13-acetate treatment had weak effects on proliferation .


Rather , tyrosine phosphorylation was shown to be directly involved in mediating CD40 -dependent signals .

Rather , tyrosine phosphorylation was shown to be directly involved in mediating <protein>CD40</protein> -dependent signals .


The use of the protein tyrosine kinase ( PTK ) -specific inhibitor herbimycin A dramatically decreased cellular proliferation without altering the activity of the human immunodeficiency virus-1 long terminal repeat ( HIV-1 LTR ) , a promoter largely dependent on the binding of nuclear factor kappa B ( NF- kappa B ) .

The use of the <protein>protein tyrosine kinase</protein> ( <protein>PTK</protein> ) -specific inhibitor herbimycin A dramatically decreased cellular proliferation without altering the activity of the <dna>human immunodeficiency virus-1 long terminal repeat</dna> ( <dna>HIV-1 LTR</dna> ) , a <dna>promoter</dna> largely dependent on the binding of <protein>nuclear factor kappa B</protein> ( <protein>NF- kappa B</protein> ) .


In contrast , the cAMP-dependent protein kinase specific inhibitor H-89 totally inhibited HIV-1 LTR activity at a concentration as low as 100 nM without affecting cellular proliferation .

In contrast , the <protein>cAMP-dependent protein kinase</protein> specific inhibitor H-89 totally inhibited <dna>HIV-1 LTR</dna> activity at a concentration as low as 100 nM without affecting cellular proliferation .


Electrophoretic mobility shift assay ( EMSA ) and supershift assay using an NF-kappa B binding sequence from the kappa light chain as a probe , revealed that both p65 ( RelA ) and c-Rel were present in CD40-stimulated B cells .

Electrophoretic mobility shift assay ( EMSA ) and supershift assay using an <dna>NF-kappa B binding sequence</dna> from the <protein>kappa light chain</protein> as a probe , revealed that both <protein>p65</protein> ( <protein>RelA</protein> ) and <protein>c-Rel</protein> were present in <cell_type>CD40-stimulated B cells</cell_type> .


While PKC depletion did not alter the NF-kappa B level , treatment of B lymphocytes with H-89 or herbimycin A provoked a decrease in the NF-kappa B level .

While <protein>PKC</protein> depletion did not alter the <protein>NF-kappa B</protein> level , treatment of <cell_type>B lymphocytes</cell_type> with H-89 or herbimycin A provoked a decrease in the <protein>NF-kappa B</protein> level .


These observations establish the importance of different signal transducing pathways leading to CD40 activation of B lymphocytes .

These observations establish the importance of different signal transducing pathways leading to <protein>CD40</protein> activation of <cell_type>B lymphocytes</cell_type> .


Interferons induce normal and aberrant retinoic-acid receptors type alpha in acute promyelocytic leukemia cells : potentiation of the induction of retinoid-dependent differentiation markers .

<protein>Interferons</protein> induce normal and aberrant <protein>retinoic-acid receptors type alpha</protein> in <cell_type>acute promyelocytic leukemia cells</cell_type> : potentiation of the induction of retinoid-dependent <protein>differentiation markers</protein> .


Treatment of the acute promyelocytic ( APL ) cell line NB4 with interferon alpha ( IFN ( alpha ) ) , as well as IFN ( beta ) and gamma , results in an increased expression of the transcripts coding for retinoic-acid receptor type alpha ( RAR ( alpha ) ) and the leukemia-specific retinoic acid receptor PML-RAR .

Treatment of the <cell_line>acute promyelocytic ( APL ) cell line</cell_line> <cell_line>NB4</cell_line> with <protein>interferon alpha</protein> ( <protein>IFN ( alpha )</protein> ) , as well as <protein>IFN ( beta ) and gamma</protein> , results in an increased expression of the transcripts coding for <protein>retinoic-acid receptor type alpha</protein> ( <protein>RAR ( alpha )</protein> ) and the <protein>leukemia-specific retinoic acid receptor</protein> <protein>PML-RAR</protein> .


Transcriptional induction of the RAR ( alpha ) and PML-RAR mRNAs is rapid and it is parallelled by an increase in the corresponding proteins .

Transcriptional induction of the <rna>RAR ( alpha ) and PML-RAR mRNAs</rna> is rapid and it is parallelled by an increase in the corresponding proteins .