Stimulation of lymphoid cells with interleukin-1beta ( IL-1beta ) led to ROI production and NF-kappaB activation , which could both be blocked by antioxidants or FLAP inhibitors , confirming that 5-LOX was the source of ROIs and was required for NF-kappaB activation in these cells .

Stimulation of <cell_type>lymphoid cells</cell_type> with <protein>interleukin-1beta</protein> ( <protein>IL-1beta</protein> ) led to ROI production and <protein>NF-kappaB</protein> activation , which could both be blocked by antioxidants or <protein>FLAP</protein> inhibitors , confirming that <protein>5-LOX</protein> was the source of ROIs and was required for <protein>NF-kappaB</protein> activation in these cells .


IL-1beta stimulation of epithelial cells did not generate any ROIs and NF-kappaB induction was not influenced by 5-LOX inhibitors .

<protein>IL-1beta</protein> stimulation of <cell_type>epithelial cells</cell_type> did not generate any ROIs and <protein>NF-kappaB</protein> induction was not influenced by <protein>5-LOX</protein> inhibitors .


However , reintroduction of a functional 5-LOX system in these cells allowed ROI production and 5-LOX -dependent NF-kappaB activation .

However , reintroduction of a functional <protein>5-LOX</protein> system in these cells allowed ROI production and <protein>5-LOX</protein> -dependent <protein>NF-kappaB</protein> activation .


In monocytic cells , IL-1beta treatment led to a production of ROIs which is independent of the 5-LOX enzyme but requires the NADPH oxidase activity .

In <cell_type>monocytic cells</cell_type> , <protein>IL-1beta</protein> treatment led to a production of ROIs which is independent of the <protein>5-LOX enzyme</protein> but requires the NADPH oxidase activity .


This pathway involves the Rac1 and Cdc42 GTPases , two enzymes which are not required for NF-kappaB activation by IL-1beta in epithelial cells .

This pathway involves the <protein>Rac1</protein> and <protein>Cdc42</protein> <protein>GTPases</protein> , two enzymes which are not required for <protein>NF-kappaB</protein> activation by <protein>IL-1beta</protein> in <cell_type>epithelial cells</cell_type> .


In conclusion , three different cell-specific pathways lead to NF-kappaB activation by IL-1beta : a pathway dependent on ROI production by 5-LOX in lymphoid cells , an ROI- and 5-LOX -independent pathway in epithelial cells , and a pathway requiring ROI production by NADPH oxidase in monocytic cells .

In conclusion , three different cell-specific pathways lead to <protein>NF-kappaB</protein> activation by <protein>IL-1beta</protein> : a pathway dependent on ROI production by <protein>5-LOX</protein> in <cell_type>lymphoid cells</cell_type> , an ROI- and <protein>5-LOX</protein> -independent pathway in <cell_type>epithelial cells</cell_type> , and a pathway requiring ROI production by <protein>NADPH oxidase</protein> in <cell_type>monocytic cells</cell_type> .


Cutting edge : dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis .

Cutting edge : dominant effect of <protein>Ile50Val variant</protein> of the <protein>human IL-4 receptor alpha-chain</protein> in <protein>IgE</protein> synthesis .


Two variants of the IL-4R alpha-chain ( IL-4Ralpha ) gene have been recently identified in association with different atopic disorders .

Two variants of the <dna>IL-4R alpha-chain ( IL-4Ralpha ) gene</dna> have been recently identified in association with different atopic disorders .


To clarify the etiological relationship between the two variants , we analyzed responsiveness to IL-4 of transfectants with four kinds of IL-4Ralpha carrying either Val or Ile at 50 and either Gln or Arg at 551 .

To clarify the etiological relationship between the two variants , we analyzed responsiveness to <protein>IL-4</protein> of transfectants with four kinds of <protein>IL-4Ralpha</protein> carrying either Val or Ile at <protein>50</protein> and either Gln or Arg at <protein>551</protein> .


The substitution of Ile for Val augmented STAT6 activation , proliferation , and transcription activity of the Iepsilon promoter by IL-4 , whereas that of Arg for Gln did not change these IL-4 signals .

The substitution of Ile for Val augmented <protein>STAT6</protein> activation , proliferation , and transcription activity of the <dna>Iepsilon promoter</dna> by <protein>IL-4</protein> , whereas that of Arg for Gln did not change these <protein>IL-4</protein> signals .


Arg551 was not associated with atopic asthma in the Japanese population .


CD23 expression and IgE synthesis by IL-4 were augmented in Ile50-bearing PBMC , compared with those bearing Val50 .

<protein>CD23</protein> expression and <protein>IgE</protein> synthesis by <protein>IL-4</protein> were augmented in <cell_line>Ile50-bearing PBMC</cell_line> , compared with those bearing Val50 .


Taken together , substitution of Arg551 does not enhance the IL-4 signal for generation of germline epsilon transcript , whereas the substitution of Ile50 contributes to enhancement of IgE synthesis .

Taken together , substitution of Arg551 does not enhance the <protein>IL-4</protein> signal for generation of germline epsilon transcript , whereas the substitution of Ile50 contributes to enhancement of <protein>IgE</protein> synthesis .


A novel growth-factor-dependent myeloid cell line derived from mouse bone marrow cells contains progenitors endowed with high proliferative potential .

A novel <cell_line>growth-factor-dependent myeloid cell line</cell_line> derived from <cell_type>mouse bone marrow cells</cell_type> contains progenitors endowed with high proliferative potential .


Constitutive expression of human colony-stimulating factor-1 receptor ( CSF-1R ) confers long-lasting CSF-1 -dependent proliferation to mouse myeloid cell lines .

Constitutive expression of <protein>human colony-stimulating factor-1 receptor</protein> ( <protein>CSF-1R</protein> ) confers long-lasting <protein>CSF-1</protein> -dependent proliferation to <cell_line>mouse myeloid cell lines</cell_line> .


We developed mice transgenic for human CSF-1R because mouse CSF-1 can not activate human CSF-1R .

We developed mice transgenic for human <protein>CSF-1R</protein> because mouse <protein>CSF-1</protein> can not activate human <protein>CSF-1R</protein> .


Then bone marrow cells from transgenic mice were plated onto MS-5 stromal cells expressing the membrane form of human CSF-1 ( 2M-1 cells ) in order to combine the hematopoietic supporting properties of stromal cells and the proliferative effects of CSF-1 .

Then <cell_type>bone marrow cells</cell_type> from transgenic mice were plated onto MS-5 stromal cells expressing the <protein>membrane form</protein> of <protein>human CSF-1</protein> ( <cell_line>2M-1 cells</cell_line> ) in order to combine the hematopoietic supporting properties of <cell_type>stromal cells</cell_type> and the proliferative effects of <protein>CSF-1</protein> .


Thus , we were able to derive a hematopoietic cell line , called 47.10 , that grew indefinitely under these conditions , whereas no cell line could be developed from nontransgenic mice .

Thus , we were able to derive a <cell_line>hematopoietic cell line</cell_line> , called <cell_line>47.10</cell_line> , that grew indefinitely under these conditions , whereas no cell line could be developed from nontransgenic mice .


Proliferation of 47.10 cells is severely affected by neutralizing anti-CSF-1R monoclonal antibodies .

Proliferation of <cell_line>47.10 cells</cell_line> is severely affected by neutralizing <protein>anti-CSF-1R monoclonal antibodies</protein> .


Morphologic and cytofluorometry analysis established that most 47.10 cells are immature myelomonocytic cells .

Morphologic and cytofluorometry analysis established that most <cell_line>47.10 cells</cell_line> are <cell_type>immature myelomonocytic cells</cell_type> .


Consistent with this phenotype , the myeloid transcription factor PU.1 , but not the erythroid transcription factor GATA-1 , is expressed in 47.10 cells .

Consistent with this phenotype , the <protein>myeloid transcription factor PU.1</protein> , but not the <protein>erythroid transcription factor GATA-1</protein> , is expressed in <cell_line>47.10 cells</cell_line> .


A few 47.10 cells ( 3-5 % ) do not express lineage specific markers ; they differentiate spontaneously to lineage-positive cells after replating on 2M-1 cells .

A few <cell_line>47.10 cells</cell_line> ( 3-5 % ) do not express lineage specific markers ; they differentiate spontaneously to <cell_line>lineage-positive cells</cell_line> after replating on <cell_line>2M-1 cells</cell_line> .


In agar cultures , 47.10 cells form 7- and 14-day colonies in response to a cocktail of granulocyte/macrophage colony-stimulating factor ( 2.5 ng/mL ) , interleukin-3 ( 1 ng/mL ) , and mouse CSF-1 ( 10 ng/mL ) .

In agar cultures , <cell_line>47.10 cells</cell_line> form 7- and 14-day colonies in response to a cocktail of <protein>granulocyte/macrophage colony-stimulating factor</protein> ( 2.5 ng/mL ) , <protein>interleukin-3</protein> ( 1 ng/mL ) , and mouse <protein>CSF-1</protein> ( 10 ng/mL ) .


Under these conditions , about 0.5 % of 47.10 cells formed large 14-day colonies ( > 1 mm ) composed of mature monocytes and granulocytes , reflecting the presence of progenitors endowed with high proliferative potential ( HPP-47.10 cells ) .

Under these conditions , about 0.5 % of <cell_line>47.10 cells</cell_line> formed large 14-day colonies ( > 1 mm ) composed of <cell_type>mature monocytes</cell_type> and <cell_type>granulocytes</cell_type> , reflecting the presence of progenitors endowed with high proliferative potential ( <cell_line>HPP-47.10 cells</cell_line> ) .


In conclusion , we have characterized a novel continuous myeloid cell line presenting a hierarchical structure similar to that of the bone marrow progenitor cell compartment .

In conclusion , we have characterized a novel <cell_line>continuous myeloid cell line</cell_line> presenting a hierarchical structure similar to that of the <cell_line>bone marrow progenitor cell compartment</cell_line> .


Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation .

Regulation of <protein>IL-4</protein> expression by the <protein>transcription factor</protein> <protein>JunB</protein> during T helper cell differentiation .


The molecular basis for restricted cytokine expression by T helper 1 ( Th1 ) and T helper 2 ( Th2 ) cells is unclear .

The molecular basis for restricted <protein>cytokine</protein> expression by <cell_type>T helper 1 ( Th1 ) and T helper 2 ( Th2 ) cells</cell_type> is unclear .


Previous studies found that P1 , an element of the interleukin 4 ( IL-4 ) promoter that binds AP-1 , is important for Th2-restricted IL-4 expression .

Previous studies found that <dna>P1</dna> , an element of the <dna>interleukin 4 ( IL-4 ) promoter</dna> that binds AP-1 , is important for Th2-restricted <protein>IL-4</protein> expression .


Here we show that JunB , but not the other Jun family members , was selectively induced in Th2 cells and not in Th1 cells during differentiation .

Here we show that <protein>JunB</protein> , but not the other <protein>Jun family members</protein> , was selectively induced in <cell_type>Th2 cells</cell_type> and not in <cell_type>Th1 cells</cell_type> during differentiation .


JunB has previously been considered to be a negative regulator of transcription .

<protein>JunB</protein> has previously been considered to be a negative regulator of transcription .


However , we show that JunB binds directly to the P1 site and synergizes with c-Maf to activate an IL-4 luciferase reporter gene .

However , we show that <protein>JunB</protein> binds directly to the <dna>P1 site</dna> and synergizes with <protein>c-Maf</protein> to activate an <dna>IL-4 luciferase reporter gene</dna> .


JunB -control of IL-4 expression is mediated by the phosphorylation of JunB at Thr102 and- 104 by JNK MAP kinase .

<protein>JunB</protein> -control of <protein>IL-4</protein> expression is mediated by the phosphorylation of <protein>JunB</protein> at Thr102 and- 104 by <protein>JNK MAP kinase</protein> .


The synergy between c-Maf and JunB can be attributed to cooperative DNA binding , which is facilitated by JunB phosphorylation .

The synergy between <protein>c-Maf</protein> and <protein>JunB</protein> can be attributed to cooperative DNA binding , which is facilitated by <protein>JunB</protein> phosphorylation .


In transgenic mice , elevated JunB levels caused increased expression of several Th2 cytokines in developing Th1 cells .

In transgenic mice , elevated <protein>JunB</protein> levels caused increased expression of several <protein>Th2 cytokines</protein> in developing <cell_type>Th1 cells</cell_type> .


JunB also upregulated IL-4 expression in response to immunization .

<protein>JunB</protein> also upregulated <protein>IL-4</protein> expression in response to immunization .


Thus , the early increase of JunB protein in Th2 cells can provide the specificity for c-Maf in IL-4 expression during T cell development and directs thereby Th2 differentiation .

Thus , the early increase of <protein>JunB</protein> protein in <cell_type>Th2 cells</cell_type> can provide the specificity for <protein>c-Maf</protein> in <protein>IL-4</protein> expression during T cell development and directs thereby Th2 differentiation .


Human T-cell leukemia virus type 1 tax protein abrogates interleukin-2 dependence in a mouse T-cell line .

<protein>Human T-cell leukemia virus type 1 tax protein</protein> abrogates <protein>interleukin-2</protein> dependence in a <cell_line>mouse T-cell line</cell_line> .


Human T-cell leukemia virus type 1 ( HTLV-1 ) is the etiologic agent of adult T-cell leukemia .


Tax , the viral protein , is thought to be crucial in the development of the disease , since it transforms healthy T cells in vitro and induces tumors in transgenic animals .

<protein>Tax</protein> , the <protein>viral protein</protein> , is thought to be crucial in the development of the disease , since it transforms <cell_type>healthy T cells</cell_type> in vitro and induces tumors in transgenic animals .


We examined the effect of Tax activity on the growth of the interleukin-2 ( IL-2 ) -dependent T-cell line CTLL-2 .

We examined the effect of <protein>Tax</protein> activity on the growth of the <cell_line>interleukin-2 ( IL-2 ) -dependent T-cell line</cell_line> <cell_line>CTLL-2</cell_line> .


Stable expression of Tax in CTLL-2 transformed cell growth from being IL-2 dependent to IL-2 independent .

Stable expression of <protein>Tax</protein> in <cell_line>CTLL-2</cell_line> transformed cell growth from being <protein>IL-2</protein> dependent to <protein>IL-2</protein> independent .


Tax stimulated transcription through NF-kappaB and the cyclic AMP-responsive element-like sequence in the HTLV-1 promoter .

<protein>Tax</protein> stimulated transcription through <protein>NF-kappaB</protein> and the <dna>cyclic AMP-responsive element-like sequence</dna> in the HTLV-1 promoter .


The finding of Tax mutants segregating these two pathways suggested that the NF-kappaB pathway was essential for IL-2 -independent growth of CTLL-2 cells while the CRE pathway was unnecessary .

The finding of <protein>Tax</protein> mutants segregating these two pathways suggested that the <protein>NF-kappaB</protein> pathway was essential for <protein>IL-2</protein> -independent growth of <cell_type>CTLL-2 cells</cell_type> while the <dna>CRE</dna> pathway was unnecessary .


However , both pathways were necessary for another transformation-related activity ( colony formation in soft agar ) of CTLL-2/Tax .

However , both pathways were necessary for another transformation-related activity ( colony formation in soft agar ) of <protein>CTLL-2/Tax</protein> .


Our results show that Tax has at least two distinct activities on T cells , and suggest that Tax plays a crucial role in IL-2 -independent T-cell transformation induced by HTLV-1 , in addition to its well-known IL-2 -dependent cell transformation .

Our results show that <protein>Tax</protein> has at least two distinct activities on <cell_type>T cells</cell_type> , and suggest that <protein>Tax</protein> plays a crucial role in <protein>IL-2</protein> -independent T-cell transformation induced by HTLV-1 , in addition to its well-known <protein>IL-2</protein> -dependent cell transformation .


Accessing Epstein-Barr virus-specific T-cell memory with peptide-loaded dendritic cells .

Accessing Epstein-Barr virus-specific T-cell memory with <cell_line>peptide-loaded dendritic cells</cell_line> .


The conventional means of studying Epstein-Barr virus ( EBV ) -induced cytotoxic T-lymphocyte ( CTL ) memory , by in vitro stimulation with the latently infected autologous lymphoblastoid cell line ( LCL ) , has important limitations .

The conventional means of studying Epstein-Barr virus ( EBV ) -induced <cell_type>cytotoxic T-lymphocyte</cell_type> ( CTL ) memory , by in vitro stimulation with the latently infected autologous <cell_line>lymphoblastoid cell line</cell_line> ( <cell_line>LCL</cell_line> ) , has important limitations .


First , it gives no information on memory to lytic cycle antigens ; second , it preferentially amplifies the dominant components of latent antigen-specific memory at the expense of key subdominant reactivities .

First , it gives no information on memory to <protein>lytic cycle antigens</protein> ; second , it preferentially amplifies the dominant components of latent antigen-specific memory at the expense of key subdominant reactivities .


Here we describe an alternative approach , based on in vitro stimulation with epitope peptide-loaded dendritic cells ( DCs ) , which allows one to probe the CTL repertoire for any individual reactivity of choice ; this method proved significantly more efficient than stimulation with peptide alone .

Here we describe an alternative approach , based on in vitro stimulation with <cell_line>epitope peptide-loaded dendritic cells</cell_line> ( <cell_line>DCs</cell_line> ) , which allows one to probe the CTL repertoire for any individual reactivity of choice ; this method proved significantly more efficient than stimulation with peptide alone .


Using this approach we first show that reactivities to the immunodominant and subdominant lytic cycle epitopes identified by T cells during primary EBV infection are regularly detectable in the CTL memory of virus carriers ; this implies that in such carriers chronic virus replication remains under direct T-cell control .

Using this approach we first show that reactivities to the immunodominant and subdominant <protein>lytic cycle epitopes</protein> identified by <cell_type>T cells</cell_type> during primary EBV infection are regularly detectable in the CTL memory of virus carriers ; this implies that in such carriers chronic virus replication remains under direct T-cell control .


We further show that subdominant latent cycle reactivities to epitopes in the latent membrane protein LMP2 , though rarely undetectable in LCL -stimulated populations , can be reactivated by DC stimulation and selectively expanded as polyclonal CTL lines ; the adoptive transfer of such preparations may be of value in targeting certain EBV-positive malignancies .

We further show that subdominant latent cycle reactivities to epitopes in the <protein>latent membrane protein LMP2</protein> , though rarely undetectable in <cell_line>LCL</cell_line> -stimulated populations , can be reactivated by DC stimulation and selectively expanded as polyclonal <cell_line>CTL lines</cell_line> ; the adoptive transfer of such preparations may be of value in targeting certain EBV-positive malignancies .


Regulation of the human interleukin-2 gene by the alpha and beta isoforms of the glucocorticoid receptor .

Regulation of the <dna>human interleukin-2 gene</dna> by the <protein>alpha and beta isoforms</protein> of the <protein>glucocorticoid receptor</protein> .


The immunosuppressive effects of glucocorticoids are largely due to transcriptional inhibition of immunologically relevant genes , such as the interleukin-2 ( IL-2 ) gene .

The immunosuppressive effects of glucocorticoids are largely due to transcriptional inhibition of <dna>immunologically relevant genes</dna> , such as the <dna>interleukin-2 ( IL-2 ) gene</dna> .


These effects are mediated by the intracellular glucocorticoid receptor ( GR ) .

These effects are mediated by the intracellular <protein>glucocorticoid receptor</protein> ( <protein>GR</protein> ) .


In humans , alternative splicing of the GR precursor mRNA gives rise to two receptor isoforms , termed GRalpha and GRbeta .

In humans , alternative splicing of the <rna>GR precursor mRNA</rna> gives rise to two receptor isoforms , termed <protein>GRalpha</protein> and <protein>GRbeta</protein> .


We previously demonstrated that GRbeta could antagonize GRalpha -mediated transactivation of a glucocorticoid-responsive element ( GRE ) -driven reporter gene in COS-7 cells .

We previously demonstrated that <protein>GRbeta</protein> could antagonize <protein>GRalpha</protein> -mediated transactivation of a <dna>glucocorticoid-responsive element ( GRE ) -driven reporter gene</dna> in <cell_line>COS-7 cells</cell_line> .


The present study was designed to analyze the roles of the two GR isoforms on glucocorticoid-mediated transrepression of the IL-2 gene .

The present study was designed to analyze the roles of the two <protein>GR isoforms</protein> on glucocorticoid-mediated transrepression of the <dna>IL-2 gene</dna> .


Using a recently developed transfection technique , we demonstrate that in primary human lymphocytes , stimulation of a 548 bp IL-2 promoter-luciferase reporter construct by phorbol ester and calcium ionophore is reversed by dexamethasone to a similar extent as in Jurkat T lymphoma cells transfected with a GRalpha expression vector .

Using a recently developed transfection technique , we demonstrate that in <cell_type>primary human lymphocytes</cell_type> , stimulation of a <dna>548 bp IL-2 promoter-luciferase reporter construct</dna> by phorbol ester and calcium ionophore is reversed by dexamethasone to a similar extent as in Jurkat T lymphoma cells transfected with a <protein>GRalpha</protein> expression vector .


Transfection of a GRbeta expression vector alone did not result in IL-2 promoter repression in response to glucocorticoids .

Transfection of a <protein>GRbeta</protein> expression vector alone did not result in <dna>IL-2 promoter</dna> repression in response to glucocorticoids .


Furthermore , GRbeta did not antagonize the repressive effects of GRalpha on IL-2 promoter activity .

Furthermore , <protein>GRbeta</protein> did not antagonize the repressive effects of <protein>GRalpha</protein> on <dna>IL-2 promoter</dna> activity .


Surprisingly , overexpression of GRbeta in Jurkat cells did not cause significant inhibition of GRalpha -induced transactivation of a GRE-dependent luciferase reporter gene either .

Surprisingly , overexpression of <protein>GRbeta</protein> in <cell_line>Jurkat cells</cell_line> did not cause significant inhibition of <protein>GRalpha</protein> -induced transactivation of a <dna>GRE-dependent luciferase reporter gene</dna> either .


We conclude that the transrepressive effect of glucocorticoids on IL-2 gene transcription is exclusively mediated by GRalpha .

We conclude that the transrepressive effect of glucocorticoids on <dna>IL-2 gene</dna> transcription is exclusively mediated by <protein>GRalpha</protein> .


GRbeta can neither antagonize GRalpha -mediated transactivation nor transrepression in Jurkat cells , indicating a cell type-specific pattern of GRbeta -mediated antiglucocorticoid activity .

<protein>GRbeta</protein> can neither antagonize <protein>GRalpha</protein> -mediated transactivation nor transrepression in <cell_line>Jurkat cells</cell_line> , indicating a cell type-specific pattern of <protein>GRbeta</protein> -mediated antiglucocorticoid activity .


Extinction of immunoglobulin gene expression in B cells upon fusion with HeLa cells is preceded by rapid nuclear depletion of essential transcription factors and is accompanied by widespread inactivation of genes expressed in a B cell-specific manner .

Extinction of <dna>immunoglobulin gene</dna> expression in <cell_type>B cells</cell_type> upon fusion with <cell_line>HeLa cells</cell_line> is preceded by rapid nuclear depletion of <protein>essential transcription factors</protein> and is accompanied by widespread inactivation of genes expressed in a B cell-specific manner .


When immunoglobulin ( Ig ) expressing B cells are fused with non-B cells , Ig expression is rapidly suppressed at the level of transcription , a phenomenon termed extinction .

When <cell_type>immunoglobulin ( Ig ) expressing B cells</cell_type> are fused with <cell_type>non-B cells</cell_type> , Ig expression is rapidly suppressed at the level of transcription , a phenomenon termed extinction .


Here we demonstrate that fusion of HeLa cells with either diploid or tetraploid B cells ( Daudi ) results in widespread extinction of several other B cell-encoded genes that are expressed in a B cell-specific manner .

Here we demonstrate that fusion of <cell_line>HeLa cells</cell_line> with either <cell_type>diploid or tetraploid B cells</cell_type> ( <cell_line>Daudi</cell_line> ) results in widespread extinction of several other <dna>B cell-encoded genes</dna> that are expressed in a B cell-specific manner .


In contrast , expression of B cell-expressed genes that are not dependent on cell-specific controls is unaffected .

In contrast , expression of <dna>B cell-expressed genes</dna> that are not dependent on cell-specific controls is unaffected .


We show that the molecular mechanism ( s ) underlying Ig gene extinction can be explained , at least in part , by a lack of transcription factors that are essential for Ig gene transcription .

We show that the molecular mechanism ( s ) underlying <dna>Ig gene</dna> extinction can be explained , at least in part , by a lack of <protein>transcription factors</protein> that are essential for <dna>Ig gene</dna> transcription .


These transcription factors are either not produced due to block of transcription of their respective genes ( Oct-2 , OBF-1 , PU.1 ) , or are rendered inactive posttranslationally ( NF-kappa B , E47 ) .

These <protein>transcription factors</protein> are either not produced due to block of transcription of their respective genes ( <dna>Oct-2</dna> , <dna>OBF-1</dna> , <protein>PU.1</protein> ) , or are rendered inactive posttranslationally ( <protein>NF-kappa B</protein> , <dna>E47</dna> ) .


By isolating Daudi x HeLa heterokaryons a few hours after fusion , we have studied the initial fate of two B cell-specific transcription factors involved in Ig gene transcription , Oct-2 and NF-kappa B .

By isolating <cell_line>Daudi x HeLa heterokaryons</cell_line> a few hours after fusion , we have studied the initial fate of two <protein>B cell-specific transcription factors</protein> involved in <dna>Ig gene</dna> transcription , <dna>Oct-2</dna> and <protein>NF-kappa B</protein> .


This report provides the first demonstration that upon fusion with HeLa cells , the nuclear contents of B cell-expressed transcription factors are depleted within a few hours with kinetics that are as fast or faster than that of Ig gene extinction .

This report provides the first demonstration that upon fusion with <cell_line>HeLa cells</cell_line> , the nuclear contents of <protein>B cell-expressed transcription factors</protein> are depleted within a few hours with kinetics that are as fast or faster than that of <dna>Ig gene</dna> extinction .


Thus , the extinguishing mechanism is effective very early after fusion .


We suggest that extinction of Ig genes is part of a global mechanism that suppresses the differentiation program foreign to the HeLa phenotype .

We suggest that extinction of <dna>Ig genes</dna> is part of a global mechanism that suppresses the differentiation program foreign to the <cell_line>HeLa phenotype</cell_line> .


Evidence for suppressed activity of the transcription factor NFAT1 at its proximal binding element P0 in the IL-4 promoter associated with enhanced IL-4 gene transcription in T cells of atopic patients .

Evidence for suppressed activity of the <protein>transcription factor</protein> <protein>NFAT1</protein> at its <dna>proximal binding element</dna> <dna>P0</dna> in the <dna>IL-4 promoter</dna> associated with enhanced <dna>IL-4 gene</dna> transcription in <cell_type>T cells</cell_type> of atopic patients .


Allergen-specific T cells in atopic patients are polarized IL-4-producing Th2 cells , promoting IgE synthesis by B cells .

Allergen-specific <cell_type>T cells</cell_type> in atopic patients are polarized <cell_line>IL-4-producing Th2 cells</cell_line> , promoting <protein>IgE</protein> synthesis by <cell_type>B cells</cell_type> .


The molecular basis for increased IL-4 gene expression in atopy is not fully understood .

The molecular basis for increased <dna>IL-4 gene</dna> expression in atopy is not fully understood .


IL-4 gene regulation in general involves the nuclear factor of activated T cells ( NFAT ) family of transcription factors , of which NFAT1 and NFAT2 are most prominent in peripheral T cells .

<dna>IL-4 gene</dna> regulation in general involves the <protein>nuclear factor of activated T cells ( NFAT ) family</protein> of <protein>transcription factors</protein> , of which <protein>NFAT1</protein> and <protein>NFAT2</protein> are most prominent in <cell_type>peripheral T cells</cell_type> .


Recently , a unique inhibitory role of NFAT1 in IL-4 gene control was shown in the mouse .

Recently , a unique inhibitory role of <protein>NFAT1</protein> in <dna>IL-4 gene</dna> control was shown in the mouse .


In a series of electrophoretic mobility shift assays with protein extracts of highly polarized Th2 clones from atopics and Th1 clones from controls we compared DNA-binding activities at the two NFAT-binding elements P0 and P1 of the crucial proximal human IL-4 promoter .

In a series of electrophoretic mobility shift assays with protein extracts of <cell_line>highly polarized Th2 clones</cell_line> from atopics and <cell_line>Th1 clones</cell_line> from controls we compared DNA-binding activities at the two <dna>NFAT-binding elements</dna> <dna>P0</dna> and <dna>P1</dna> of the crucial proximal human <dna>IL-4 promoter</dna> .


At the most proximal P0 site , NFAT-containing complexes devoid of NFAT2 were readily inducible in the Th1 clones , but hardly or not in the Th2 clones .

At the most proximal <dna>P0</dna> site , NFAT-containing complexes devoid of <protein>NFAT2</protein> were readily inducible in the <cell_line>Th1 clones</cell_line> , but hardly or not in the <cell_line>Th2 clones</cell_line> .


In contrast , both in Th1 and Th2 clones NFAT-containing complexes were strongly inducible at the P1 site , consisting of NFAT2 and a P0 -compatible NFAT activity , without apparent differences between Th1 and Th2 clones .

In contrast , both in <cell_line>Th1 and Th2 clones</cell_line> NFAT-containing complexes were strongly inducible at the <dna>P1 site</dna> , consisting of <protein>NFAT2</protein> and a <dna>P0</dna> -compatible <protein>NFAT</protein> activity , without apparent differences between <cell_line>Th1 and Th2 clones</cell_line> .


Like in Th2 clones , suppressed NFAT- P0 complex formation was observed also at the polyclonal level in peripheral blood mononuclear cells ( PBMC ) of three of five severe atopic dermatitis patients with strongly elevated serum IgE levels , but not in control PBMC .

Like in <cell_line>Th2 clones</cell_line> , suppressed NFAT- <dna>P0</dna> complex formation was observed also at the polyclonal level in <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) of three of five severe atopic dermatitis patients with strongly elevated serum <protein>IgE</protein> levels , but not in control <cell_type>PBMC</cell_type> .


These findings suggest that high-level IL-4 production in atopic Th2 cells is associated with selective reduction of suppressive NFAT1 activity at the IL-4 P0 element and that some patients with this multifactorial disease may have a putative systemic disorder at this level .

These findings suggest that high-level <protein>IL-4</protein> production in <cell_type>atopic Th2 cells</cell_type> is associated with selective reduction of suppressive <protein>NFAT1</protein> activity at the <dna>IL-4 P0 element</dna> and that some patients with this multifactorial disease may have a putative systemic disorder at this level .


Differential expression and phosphorylation of CTCF , a c-myc transcriptional regulator , during differentiation of human myeloid cells .

Differential expression and phosphorylation of <protein>CTCF</protein> , a c-myc transcriptional regulator , during differentiation of human myeloid cells .


CTCF is a transcriptional repressor of the c-myc gene .

<protein>CTCF</protein> is a transcriptional repressor of the c-myc gene .


Although CTCF has been characterized in some detail , there is very little information about the regulation of CTCF activity .

Although <protein>CTCF</protein> has been characterized in some detail , there is very little information about the regulation of <protein>CTCF</protein> activity .


Therefore we investigated CTCF expression and phosphorylation during induced differentiation of human myeloid leukemia cells .

Therefore we investigated <protein>CTCF</protein> expression and phosphorylation during induced differentiation of <cell_type>human myeloid leukemia cells</cell_type> .


We found that : ( i ) both CTCF mRNA and protein are down-regulated during terminal differentiation in most cell lines tested ; ( ii ) CTCF down-regulation is retarded and less pronounced than that of c-myc ; ( iii ) CTCF protein is differentially phosphorylated and the phosphorylation profiles depend on the differentiation pathway .

We found that : ( i ) both <rna>CTCF mRNA</rna> and protein are down-regulated during terminal differentiation in most cell lines tested ; ( ii ) <protein>CTCF</protein> down-regulation is retarded and less pronounced than that of <dna>c-myc</dna> ; ( iii ) <protein>CTCF protein</protein> is differentially phosphorylated and the phosphorylation profiles depend on the differentiation pathway .


We concluded that CTCF expression and activity is controlled at transcriptional and post-transcriptional levels .

We concluded that <protein>CTCF</protein> expression and activity is controlled at transcriptional and post-transcriptional levels .


Glucocorticoid resistance in the squirrel monkey is associated with overexpression of the immunophilin FKBP51 .

Glucocorticoid resistance in the squirrel monkey is associated with overexpression of the <protein>immunophilin FKBP51</protein> .


Squirrel monkeys are neotropical primates that have high circulating cortisol to compensate for expression of glucocorticoid receptors ( GRs ) with reduced affinity .

Squirrel monkeys are neotropical primates that have high circulating cortisol to compensate for expression of <protein>glucocorticoid receptors</protein> ( <protein>GRs</protein> ) with reduced affinity .


The low binding affinity of squirrel monkey GR does not result from substitutions in the receptor , because squirrel monkey GR expressed in vitro exhibits high affinity .

The low binding affinity of squirrel monkey <protein>GR</protein> does not result from substitutions in the receptor , because <protein>squirrel monkey GR</protein> expressed in vitro exhibits high affinity .


Rather , squirrel monkeys express a soluble factor that , in mixing studies of cytosol from squirrel monkey lymphocytes ( SML ) and mouse L929 cells , reduced GR binding affinity by 11-fold .

Rather , squirrel monkeys express a soluble factor that , in mixing studies of cytosol from <cell_type>squirrel monkey lymphocytes</cell_type> ( <cell_type>SML</cell_type> ) and mouse L929 cells , reduced GR binding affinity by 11-fold .


In an effort to identify this factor , the cellular levels of components of the GR heterocomplex in SML and human lymphocytes ( HL ) were compared .

In an effort to identify this factor , the cellular levels of components of the <protein>GR heterocomplex</protein> in <cell_type>SML</cell_type> and <cell_type>human lymphocytes</cell_type> ( <cell_type>HL</cell_type> ) were compared .


The immunophilin FKBP51 was 13-fold higher in SML than in HL cytosol ; FKBP52 in SML was 42 % of that in HL cytosol .

The <protein>immunophilin FKBP51</protein> was 13-fold higher in <cell_type>SML</cell_type> than in HL cytosol ; <protein>FKBP52</protein> in <cell_type>SML</cell_type> was 42 % of that in HL cytosol .


A role for changes in immunophilins , causing glucocorticoid resistance in neotropical primates , is supported by the following : the changes in FKBP51 and FKBP52 were observed in cells from other neotropical primates with glucocorticoid resistance ; the elevated level of FKBP51 was reflected in an abundance of FKBP51 in heat shock protein 90 complexes in SML ; when cytosols of SML and L929 cells were mixed , the decrease in GR binding was associated with incorporation of FKBP51 into GR heterocomplexes ; the effect of SML cytosol on GR binding was reproduced with cytosol from COS cells expressing squirrel monkey FKBP51 ; and both the effect of SML cytosol on GR binding and the incorporation of FKBP51 into GR heterocomplexes were blocked by FK506 .

A role for changes in <protein>immunophilins</protein> , causing glucocorticoid resistance in neotropical primates , is supported by the following : the changes in <protein>FKBP51</protein> and <protein>FKBP52</protein> were observed in cells from other neotropical primates with glucocorticoid resistance ; the elevated level of <protein>FKBP51</protein> was reflected in an abundance of <protein>FKBP51</protein> in <protein>heat shock protein 90 complexes</protein> in <cell_type>SML</cell_type> ; when cytosols of <cell_type>SML</cell_type> and <cell_line>L929 cells</cell_line> were mixed , the decrease in GR binding was associated with incorporation of <protein>FKBP51</protein> into <protein>GR heterocomplexes</protein> ; the effect of <cell_type>SML</cell_type> cytosol on GR binding was reproduced with cytosol from <cell_line>COS cells</cell_line> expressing squirrel monkey <protein>FKBP51</protein> ; and both the effect of <cell_type>SML</cell_type> cytosol on GR binding and the incorporation of <protein>FKBP51</protein> into <protein>GR heterocomplexes</protein> were blocked by FK506 .


Regulation of GR binding by FKBP51 represents a previously unrecognized mechanism for regulating glucocorticoid sensitivity .

Regulation of GR binding by <protein>FKBP51</protein> represents a previously unrecognized mechanism for regulating glucocorticoid sensitivity .


High-level replication of human immunodeficiency virus in thymocytes requires NF-kappaB activation through interaction with thymic epithelial cells .

High-level replication of human immunodeficiency virus in <cell_type>thymocytes</cell_type> requires <protein>NF-kappaB</protein> activation through interaction with <cell_type>thymic epithelial cells</cell_type> .


We have previously demonstrated that interaction of infected thymocytes with autologous thymic epithelial cells ( TEC ) is a prerequisite for a high level of human immunodeficiency virus type 1 ( HIV-1 ) replication in thymocytes ( M.Rothe , L.Chene , M.Nugeyre , F.Barre-Sinoussi , and N.Israel , J.Virol.72 : 5852-5861 , 1998 ) .

We have previously demonstrated that interaction of infected <cell_type>thymocytes</cell_type> with autologous <cell_type>thymic epithelial cells</cell_type> ( <cell_type>TEC</cell_type> ) is a prerequisite for a high level of human immunodeficiency virus type 1 ( HIV-1 ) replication in <cell_type>thymocytes</cell_type> ( M.Rothe , L.Chene , M.Nugeyre , F.Barre-Sinoussi , and N.Israel , J.Virol.72 : 5852-5861 , 1998 ) .


We report here that this activation of HIV replication takes place at the transcriptional level through activation of the Rel/NF-kappaB transcription factors .

We report here that this activation of HIV replication takes place at the transcriptional level through activation of the <protein>Rel/NF-kappaB</protein> <protein>transcription factors</protein> .


We first demonstrate that an HIV-1 provirus ( SF-2 strain ) very effectively replicates in thymocytes cocultured with TEC whereas this provirus , with kappaB sites deleted , fails to replicate .

We first demonstrate that an HIV-1 provirus ( SF-2 strain ) very effectively replicates in <cell_type>thymocytes</cell_type> cocultured with <cell_type>TEC</cell_type> whereas this provirus , with <dna>kappaB sites</dna> deleted , fails to replicate .


We provide evidence that several NF-kappaB complexes are constitutively found in the nuclei of thymocytes either freshly isolated from the thymus or maintained in coculture with autologous or heterologous TEC .

We provide evidence that several <protein>NF-kappaB complexes</protein> are constitutively found in the nuclei of <cell_type>thymocytes</cell_type> either freshly isolated from the thymus or maintained in coculture with autologous or heterologous <cell_type>TEC</cell_type> .


The prevalent complex is the heterodimer p50-p65 .

The prevalent complex is the <protein>heterodimer p50-p65</protein> .


NF-kappaB activity is tightly correlated with the transcriptional activity of a long terminal repeat ( LTR ) of HIV-1 transfected in thymocytes .

<protein>NF-kappaB</protein> activity is tightly correlated with the transcriptional activity of a <dna>long terminal repeat</dna> ( <dna>LTR</dna> ) of HIV-1 transfected in <cell_type>thymocytes</cell_type> .


The cotransfection of this LTR with a mutated IkappaBalpha molecule formally demonstrates that LTR transactivation is regulated by members of the Rel/NF-kappaB family in thymocytes .

The cotransfection of this <dna>LTR</dna> with a mutated <protein>IkappaBalpha molecule</protein> formally demonstrates that <dna>LTR</dna> transactivation is regulated by members of the <protein>Rel/NF-kappaB family</protein> in <cell_type>thymocytes</cell_type> .


We also showed that tumor necrosis factor ( TNF ) and to a lesser extent interleukin-1 ( IL-1 ) , secreted within the coculture , induce NF-kappaB activity and a correlative LTR transactivation .

We also showed that <protein>tumor necrosis factor</protein> ( <protein>TNF</protein> ) and to a lesser extent <protein>interleukin-1</protein> ( <protein>IL-1</protein> ) , secreted within the coculture , induce <protein>NF-kappaB</protein> activity and a correlative <dna>LTR</dna> transactivation .


However IL-7 , a crucial factor for thymopoiesis that is secreted mainly by TEC , is a necessary cofactor for NF-kappaB activation elicited by TNF or IL-1 .

However <protein>IL-7</protein> , a crucial factor for thymopoiesis that is secreted mainly by <cell_type>TEC</cell_type> , is a necessary cofactor for <protein>NF-kappaB</protein> activation elicited by <protein>TNF</protein> or <protein>IL-1</protein> .


Together , these data indicate that NF-kappaB activation , required for a high level of HIV replication in thymocytes , is regulated in a specific manner in the thymic microenvironment which provides the necessary cytokines : TNF , IL-1 , and IL-7 .

Together , these data indicate that <protein>NF-kappaB</protein> activation , required for a high level of HIV replication in <cell_type>thymocytes</cell_type> , is regulated in a specific manner in the thymic microenvironment which provides the necessary cytokines : <protein>TNF</protein> , <protein>IL-1</protein> , and <protein>IL-7</protein> .


Imbalanced expression of the glucocorticoid receptor isoforms in cultured lymphocytes from a patient with systemic glucocorticoid resistance and chronic lymphocytic leukemia .

Imbalanced expression of the <protein>glucocorticoid receptor isoforms</protein> in <cell_type>cultured lymphocytes</cell_type> from a patient with systemic glucocorticoid resistance and chronic lymphocytic leukemia .


The human glucocorticoid receptor ( GR ) is expressed as two alternatively spliced isoforms , GRalpha and GRbeta .

The <protein>human glucocorticoid receptor</protein> ( <protein>GR</protein> ) is expressed as two alternatively spliced isoforms , <protein>GRalpha</protein> and <protein>GRbeta</protein> .


Whereas GRalpha is a hormone-activated transcription factor , GRbeta does not bind glucocorticoids ( GCs ) , is transcriptionally inactive , and is a potential inhibitor of activated GRalpha .

Whereas <protein>GRalpha</protein> is a hormone-activated <protein>transcription factor</protein> , <protein>GRbeta</protein> does not bind glucocorticoids ( GCs ) , is transcriptionally inactive , and is a potential inhibitor of activated <protein>GRalpha</protein> .


Differential expression of GR isoforms may play a role in generalized or tissue-specific GC resistance .

Differential expression of <protein>GR isoforms</protein> may play a role in generalized or tissue-specific GC resistance .


GCs induce apoptosis in neoplastic lymphoid cells ; and , defective apoptosis is implicated in the genesis of chronic lymphocytic leukemia ( CLL ) .

GCs induce apoptosis in <cell_type>neoplastic lymphoid cells</cell_type> ; and , defective apoptosis is implicated in the genesis of chronic lymphocytic leukemia ( CLL ) .


We studied a patient with generalized GC resistance and CLL .


GR number in the patient 's transformed lymphocytes was approximately one half that of control cells with a approximately 10-fold reduction in binding affinity for dexamethasone .

GR number in the patient 's <cell_line>transformed lymphocytes</cell_line> was approximately one half that of control cells with a approximately 10-fold reduction in binding affinity for dexamethasone .


In vitro apoptosis induction in CLL cells was delayed in response to GCs , but not to other apoptosis inducers .

In vitro apoptosis induction in <cell_line>CLL cells</cell_line> was delayed in response to GCs , but not to other apoptosis inducers .


Sequencing of the GR cDNA and gene including the 2.3-kb coding region , the intron/exon junctions , the known 5'-regulatory region , and approximately 300 bp of the 3'-region revealed no alterations .

Sequencing of the <dna>GR cDNA</dna> and gene including the 2.3-kb coding region , the intron/exon junctions , the known <dna>5'-regulatory region</dna> , and approximately 300 bp of the <dna>3'-region</dna> revealed no alterations .


Western blot with an N-terminal antibody showed normal levels of immunoreactive GR , but quantitative analysis with isoform-specific C-terminal antibodies revealed a markedly reduced GRalpha expression , and high GRbeta expression .

Western blot with an N-terminal antibody showed normal levels of <protein>immunoreactive GR</protein> , but quantitative analysis with isoform-specific <protein>C-terminal antibodies</protein> revealed a markedly reduced <protein>GRalpha</protein> expression , and high <protein>GRbeta</protein> expression .


These findings indicate that imbalanced expression of the GR isoforms may be a mechanism of GC resistance , and may have implications for tumorigenesis by enhancing cell survival .

These findings indicate that imbalanced expression of the <protein>GR isoforms</protein> may be a mechanism of GC resistance , and may have implications for tumorigenesis by enhancing cell survival .


Copyright 1999 Academic Press .


Intranuclear targeted delivery of functional NF-kappaB by 70 kDa heat shock protein .

Intranuclear targeted delivery of functional <protein>NF-kappaB</protein> by <protein>70 kDa heat shock protein</protein> .


The 70 kDa heat shock protein ( Hsp70 ) is a highly conserved , ubiquitous protein involved in chaperoning proteins to various cellular organelles .

The <protein>70 kDa heat shock protein</protein> ( <protein>Hsp70</protein> ) is a highly conserved , <protein>ubiquitous protein</protein> involved in <protein>chaperoning proteins</protein> to various cellular organelles .


Here we show that when added exogenously to cells , Hsp70 is readily imported into both cytoplasmic and nuclear compartments in a cell-type-specific fashion .

Here we show that when added exogenously to cells , <protein>Hsp70</protein> is readily imported into both cytoplasmic and nuclear compartments in a cell-type-specific fashion .


We exploited this ability of Hsp70 to deliver NF-kappaB , a key transcriptional regulator of inflammatory responses .

We exploited this ability of <protein>Hsp70</protein> to deliver <protein>NF-kappaB</protein> , a key transcriptional regulator of inflammatory responses .


We demonstrate that a fusion protein composed of a C-terminal Hsp70 peptide and the p50 subunit of NF-kappaB was directed into the nucleus of cells , could bind DNA specifically , and activated Igkappa expression and TNFalpha production .

We demonstrate that a fusion protein composed of a C-terminal <protein>Hsp70</protein> peptide and the <protein>p50 subunit</protein> of <protein>NF-kappaB</protein> was directed into the nucleus of cells , could bind DNA specifically , and activated <protein>Igkappa</protein> expression and <protein>TNFalpha</protein> production .


We therefore propose that Hsp70 can be used as a vehicle for intracytoplasmic and intranuclear delivery of proteins or DNA to modulate gene expression and thereby control immune responses .

We therefore propose that <protein>Hsp70</protein> can be used as a vehicle for intracytoplasmic and intranuclear delivery of proteins or DNA to modulate gene expression and thereby control immune responses .


Characterization of the human elk-1 promoter .

Characterization of the <dna>human elk-1 promoter</dna> .


Potential role of a downstream intronic sequence for elk-1 gene expression in monocytes .

Potential role of a <dna>downstream intronic sequence</dna> for <dna>elk-1 gene</dna> expression in <cell_type>monocytes</cell_type> .


To characterize the human elk-1 promoter , we mapped the transcriptional start site and isolated elk-1-specific genomic phage clones that contained extensive upstream and downstream sequences .

To characterize the <dna>human elk-1 promoter</dna> , we mapped the <dna>transcriptional start site</dna> and isolated <cell_line>elk-1-specific genomic phage clones</cell_line> that contained extensive <dna>upstream and downstream sequences</dna> .


A TATA-like motif was identified immediately upstream of the transcriptional start site .

A <dna>TATA-like motif</dna> was identified immediately upstream of the <dna>transcriptional start site</dna> .


Functional analyses of DNA fragments containing the TATA element and the identification of a DNase I-hypersensitive chromatin site ( HS 1 ) in close proximity to the TATA box suggest that the identified TATA motif is important for elk-1 transcription in vivo .

Functional analyses of <dna>DNA fragments</dna> containing the <dna>TATA element</dna> and the identification of a <dna>DNase I-hypersensitive chromatin site</dna> ( <dna>HS 1</dna> ) in close proximity to the <dna>TATA box</dna> suggest that the identified <dna>TATA motif</dna> is important for <dna>elk-1</dna> transcription in vivo .


Sequences upstream and downstream from the TATA box were found to contribute to elk-1 promoter activity .

Sequences upstream and downstream from the <dna>TATA box</dna> were found to contribute to <dna>elk-1</dna> promoter activity .


A second hypersensitive site ( HS 2 ) was identified within the first intron in pre-monocytic cells , which express Elk-1 only when differentiating to monocytes .

A second hypersensitive site ( HS 2 ) was identified within the first intron in pre-monocytic cells , which express Elk-1 only when differentiating to <cell_type>monocytes</cell_type> .


In a variety of other cell types , which display a constitutive Elk-1 expression , HS 2 did not exist , suggesting that inducibility of elk-1 expression is associated with the presence of HS 2 .

In a variety of other cell types , which display a constitutive <protein>Elk-1</protein> expression , HS 2 did not exist , suggesting that inducibility of <dna>elk-1</dna> expression is associated with the presence of HS 2 .


Egr-1 and the serum response factor were found to interact specifically with the intronic sequence at +265 and +448 , respectively .

Egr-1 and the serum response factor were found to interact specifically with the <dna>intronic sequence</dna> at +265 and +448 , respectively .


Because Egr-1 mRNA and protein levels were observed to increase significantly before induction of elk-1 expression , we propose that Egr-1 is important for the regulation of elk-1 transcription in differentiating monocytes .

Because <rna>Egr-1 mRNA</rna> and protein levels were observed to increase significantly before induction of <dna>elk-1</dna> expression , we propose that <protein>Egr-1</protein> is important for the regulation of <dna>elk-1</dna> transcription in differentiating <cell_type>monocytes</cell_type> .


Immunohistochemical study of c-fos-positive lymphocytes infiltrated into human squamous cell carcinomas of the head and neck during radiation therapy and its clinical significance .

Immunohistochemical study of <protein>c-fos-positive lymphocytes</protein> infiltrated into human squamous cell carcinomas of the head and neck during radiation therapy and its clinical significance .


C-fos has been reported to be one of the immediate early genes in signal transduction systems after many kinds of stresses , including ionizing radiation .

<dna>C-fos</dna> has been reported to be one of the <dna>immediate early genes</dna> in signal transduction systems after many kinds of stresses , including ionizing radiation .


Changes in c-fos expression induced by radiation therapy in tumor tissues have not yet been reported .

Changes in <dna>c-fos</dna> expression induced by radiation therapy in tumor tissues have not yet been reported .


In this study , we have attempted to determine whether c-fos expression is induced by radiotherapy in human squamous cell carcinomas of the head and neck and to establish a possible correlation between c-fos expression and the therapeutic effects of radiation therapy .

In this study , we have attempted to determine whether <dna>c-fos</dna> expression is induced by radiotherapy in human squamous cell carcinomas of the head and neck and to establish a possible correlation between <dna>c-fos</dna> expression and the therapeutic effects of radiation therapy .


Twenty-seven patients with tumors of the oral cavity , oropharynx , and maxillary sinus were examined , all of which were confirmed as squamous cell carcinomas .


After obtaining the patients ' informed consent , biopsies were performed before treatment and at doses of 4 , 10 , and 20 Gy of radiotherapy , and the specimens were preserved in liquid nitrogen for further examination .


Serial sectioning of 6 micrometer was performed using a cryostat , and samples were immunohistochemically stained using the streptoavidin -biotin peroxidase method and a monoclonal antibody against c-fos .

Serial sectioning of 6 micrometer was performed using a cryostat , and samples were immunohistochemically stained using the <protein>streptoavidin</protein> <protein>-biotin peroxidase</protein> method and a monoclonal antibody against c-fos .


Three of the 27 patients with squamous cell carcinoma showed slight expression of c-fos in their tumor cells before and/or at 4 or 10 Gy of radiotherapy .


The tumors showed high radiosensitivity .


Concerning tumor-infiltrating lymphocytes , the rate of moderate or remarkable grades of c-fos-positive lymphocytes before radiotherapy and at radiation doses of 4 , 10 , and 20 Gy was 8.0 , 29.2 , 4.8 , and 0 % , respectively .

Concerning <cell_type>tumor-infiltrating lymphocytes</cell_type> , the rate of moderate or remarkable grades of <protein>c-fos-positive lymphocytes</protein> before radiotherapy and at radiation doses of 4 , 10 , and 20 Gy was 8.0 , 29.2 , 4.8 , and 0 % , respectively .


The relationship between the immunohistochemical findings and the antitumor effect at a radiation dose of 20 Gy was examined on the corresponding H & E-stained sections .


In patients whose infiltration of c-fos-positive lymphocytes into tumor tissues were moderate or remarkable at 4 Gy of radiotherapy , the tumors responded significantly well to radiation therapy ( P < 0.025 , chi2 test ) , and the patients took a significantly favorable clinical course ( P < 0.05 , chi2 test ) .

In patients whose infiltration of <protein>c-fos-positive lymphocytes</protein> into tumor tissues were moderate or remarkable at 4 Gy of radiotherapy , the tumors responded significantly well to radiation therapy ( P < 0.025 , chi2 test ) , and the patients took a significantly favorable clinical course ( P < 0.05 , chi2 test ) .


In a sample from one of the patients , c-fos-positive lymphocytes were identified as CD4 positive and CD8 negative .

In a sample from one of the patients , <protein>c-fos-positive lymphocytes</protein> were identified as CD4 positive and CD8 negative .


Therefore , the high radiosensitivity of squamous cell carcinomas in our samples could be explained by an overexpression of c-fos in the tumor-infiltrating lymphocytes induced by small doses of radiation therapy , and these activated lymphocytes exerted a cytotoxic effect against the cancer cells .

Therefore , the high radiosensitivity of squamous cell carcinomas in our samples could be explained by an overexpression of <protein>c-fos</protein> in the <cell_type>tumor-infiltrating lymphocytes</cell_type> induced by small doses of radiation therapy , and these <cell_type>activated lymphocytes</cell_type> exerted a cytotoxic effect against the <cell_type>cancer cells</cell_type> .


Paternal expression of WT1 in human fibroblasts and lymphocytes .

Paternal expression of <protein>WT1</protein> in <cell_type>human fibroblasts</cell_type> and <cell_type>lymphocytes</cell_type> .


The Wilms ' tumor suppressor gene ( WT1 ) was previously identified as being imprinted , with frequent maternal expression in human placentae and fetal brains .

The <dna>Wilms ' tumor suppressor gene</dna> ( <protein>WT1</protein> ) was previously identified as being imprinted , with frequent maternal expression in human placentae and fetal brains .


We examined the allele-specific expression of WT1 in cultured human fibroblasts from 15 individuals .

We examined the allele-specific expression of <protein>WT1</protein> in cultured <cell_type>human fibroblasts</cell_type> from 15 individuals .


Seven of 15 fibroblast lines were heterozygous for polymorphic alleles , and the expression patterns were variable , i.e. , equal , unequal or monoallelic paternal expression in three , two and two cases , respectively .

Seven of 15 <cell_line>fibroblast lines</cell_line> were heterozygous for <dna>polymorphic alleles</dna> , and the expression patterns were variable , i.e. , equal , unequal or monoallelic paternal expression in three , two and two cases , respectively .


Exclusive paternal expression of WT1 was also shown in non-cultured peripheral lymphocytes from the latter two individuals .

Exclusive paternal expression of <protein>WT1</protein> was also shown in <cell_type>non-cultured peripheral lymphocytes</cell_type> from the latter two individuals .


The allele-specific expression profiles of other imprinted genes , IGF2 and H19 , on human chromosome 11 were constant and consistent with those in other tissues .

The allele-specific expression profiles of other <dna>imprinted genes</dna> , <dna>IGF2</dna> and <dna>H19</dna> , on <dna>human chromosome 11</dna> were constant and consistent with those in other tissues .


Our unexpected observations of paternal or biallelic expression of WT1 in fibroblasts and lymphocytes , together with the previous findings of maternal or biallelic expression in placentae and brains , suggest that the allele-specific regulatory system of WT1 is unique and may be controlled by a putative tissue- and individual-specific modifier .

Our unexpected observations of paternal or biallelic expression of <protein>WT1</protein> in <cell_type>fibroblasts</cell_type> and <cell_type>lymphocytes</cell_type> , together with the previous findings of maternal or biallelic expression in placentae and brains , suggest that the allele-specific regulatory system of <protein>WT1</protein> is unique and may be controlled by a putative tissue- and individual-specific modifier .


T cell reactivity to Sjogren 's syndrome related antigen La ( SSB ) .

T cell reactivity to Sjogren 's syndrome related antigen <protein>La ( SSB )</protein> .


OBJECTIVE .


Many patients with primary Sjogren 's syndrome ( SS ) make high titer IgG autoantibodies to the La ( SSB ) antigen , suggesting antigen specific T cell-B cell interactions .

Many patients with primary Sjogren 's syndrome ( SS ) make high titer <protein>IgG autoantibodies</protein> to the <protein>La ( SSB )</protein> antigen , suggesting antigen specific T cell-B cell interactions .


T cell responses to some nuclear antigens , particularly U1RNP , have been detected in patients with systemic lupus erythematosus ( SLE ) and in healthy subjects .

T cell responses to some nuclear antigens , particularly <protein>U1RNP</protein> , have been detected in patients with systemic lupus erythematosus ( SLE ) and in healthy subjects .


We investigated T cell reactivity to the autoantigen SSB in patients with SS and healthy controls .

We investigated T cell reactivity to the <protein>autoantigen SSB</protein> in patients with SS and healthy controls .


METHODS .


Using the [ 3H ] thymidine proliferation assay , we determined reactivity to purified recombinant SSB ( rSSB ) in 20 patients with SS and 19 controls .

Using the [ 3H ] thymidine proliferation assay , we determined reactivity to <protein>purified recombinant SSB</protein> ( <protein>rSSB</protein> ) in 20 patients with SS and 19 controls .


Specificity was determined using tetanus toxoid , endotoxin , and 3 other autoantigens ( PBC.M2 , Sc170 , and GAD ) .

Specificity was determined using tetanus toxoid , endotoxin , and 3 other <protein>autoantigens</protein> ( <protein>PBC.M2</protein> , <protein>Sc170</protein> , and <protein>GAD</protein> ) .


Precursor frequency was calculated by limiting dilution analysis .


HLA Class II dependency was investigated using anti-Class II monoclonal antibodies .

HLA Class II dependency was investigated using <protein>anti-Class II monoclonal antibodies</protein> .


HLA-DR typing was by polymerase chain reaction and sequence specific oligonucleotide typing .


RESULTS .


Six of 20 patients with SS and 10/19 controls proliferated to La ( rSSB ) .

Six of 20 patients with SS and 10/19 controls proliferated to La ( <protein>rSSB</protein> ) .


Precursor frequency of anti-SSB T cells was 1 : 77 , 040 and 1 : 115 , 000 in 2 healthy subjects and 1 : 230 , 250 and 1 : 103 , 034 in two patients with SS .

Precursor frequency of <cell_line>anti-SSB T cells</cell_line> was 1 : 77 , 040 and 1 : 115 , 000 in 2 healthy subjects and 1 : 230 , 250 and 1 : 103 , 034 in two patients with SS .


Anti- HLA-DR abrogated proliferation to SSB and tetanus toxoid .

Anti- <protein>HLA-DR</protein> abrogated proliferation to <protein>SSB</protein> and tetanus toxoid .


Thirteen of 15 patients with SS and 4/17 controls were HLA-DR3 positive , with no apparent association of HLA-DR3 with SSB reactivity in controls .

Thirteen of 15 patients with SS and 4/17 controls were <protein>HLA-DR3</protein> positive , with no apparent association of <protein>HLA-DR3</protein> with <protein>SSB</protein> reactivity in controls .


CONCLUSION .


Anti-La ( SSB ) specific T cells occur in a significant proportion of controls and in some patients with SS .

<cell_line>Anti-La ( SSB ) specific T cells</cell_line> occur in a significant proportion of controls and in some patients with SS .


The function of SSB T cells in controls remains to be defined .

The function of <cell_line>SSB T cells</cell_line> in controls remains to be defined .


They may represent immunoregulatory cells , and further analysis of these cells , and a comparison to those found in patients with SS , may elucidate normal immunoregulation and the derangements that lead to Sjogren 's syndrome .

They may represent <cell_type>immunoregulatory cells</cell_type> , and further analysis of these cells , and a comparison to those found in patients with SS , may elucidate normal immunoregulation and the derangements that lead to Sjogren 's syndrome .


Anti-rheumatic compound aurothioglucose inhibits tumor necrosis factor-alpha -induced HIV-1 replication in latently infected OM10.1 and Ach2 cells .

Anti-rheumatic compound aurothioglucose inhibits <protein>tumor necrosis factor-alpha</protein> -induced HIV-1 replication in latently infected <cell_line>OM10.1 and Ach2 cells</cell_line> .


NF-kappaB is a potent cellular activator of HIV-1 gene expression .

<protein>NF-kappaB</protein> is a potent cellular activator of HIV-1 gene expression .


Down-regulation of NF-kappaB activation is known to inhibit HIV replication from the latently infected cells .

Down-regulation of <protein>NF-kappaB</protein> activation is known to inhibit HIV replication from the <cell_type>latently infected cells</cell_type> .


Gold compounds have been effectively used for many decades in the treatment of rheumatoid arthritis .


We previously reported that gold compounds , especially aurothioglucose ( AuTG ) containing monovalent gold ion , inhibited the DNA-binding of NF-kappaB in vitro .

We previously reported that gold compounds , especially aurothioglucose ( AuTG ) containing monovalent gold ion , inhibited the DNA-binding of <protein>NF-kappaB</protein> in vitro .


In this report we have examined the efficacy of the gold compound AuTG as an inhibitor of HIV replication in latently infected OM10.1 and Ach2 cells .

In this report we have examined the efficacy of the gold compound AuTG as an inhibitor of HIV replication in latently infected <cell_line>OM10.1 and Ach2 cells</cell_line> .


Tumor necrosis factor ( TNF ) -alpha -induced HIV-1 replication in OM10.1 or Ach2 cells was significantly inhibited by non-cytotoxic doses of AuTG ( > 10 microM in OM10.1 cells and > 25 F.M in Ach2 cells ) , while 25 microM of the counter-anion thioglucose ( TG ) or gold compound containing divalent gold ion , HAuCl3 , had no effect .

<protein>Tumor necrosis factor ( TNF ) -alpha</protein> -induced HIV-1 replication in <cell_line>OM10.1</cell_line> or <cell_line>Ach2 cells</cell_line> was significantly inhibited by non-cytotoxic doses of AuTG ( > 10 microM in OM10.1 cells and > 25 F.M in <cell_line>Ach2 cells</cell_line> ) , while 25 microM of the <protein>counter-anion thioglucose</protein> ( <protein>TG</protein> ) or gold compound containing divalent gold ion , HAuCl3 , had no effect .


The effect of AuTG on NF-kappaB -dependent gene expression was confirmed by a transient CAT assay .

The effect of AuTG on <protein>NF-kappaB</protein> -dependent gene expression was confirmed by a transient <protein>CAT</protein> assay .


Specific staining as well as electron microscopic examinations revealed the accumulation of metal gold in the cells , supporting our previous hypothesis that gold ions could block NF-kappaB -DNA binding by a redox mechanism .

Specific staining as well as electron microscopic examinations revealed the accumulation of metal gold in the cells , supporting our previous hypothesis that gold ions could block <protein>NF-kappaB</protein> -DNA binding by a redox mechanism .


These observations indicate that the monovalent gold compound AuTG is a potentially useful drug for the treatment of patients infected with HIV .


Clonality of isolated eosinophils in the hypereosinophilic syndrome .

Clonality of <cell_type>isolated eosinophils</cell_type> in the hypereosinophilic syndrome .


The idiopathic hypereosinophilic syndrome ( IHES ) is a rare disorder characterized by unexplained , persistent eosinophilia associated with multiple organ dysfunction due to eosinophilic tissue infiltration .


In the absence of karyotypic abnormalities , there is no specific test to detect clonal eosinophilia in IHES .


Analysis of X-chromosome inactivation patterns can be used to determine whether proliferative disorders are clonal in origin .

Analysis of <dna>X-chromosome</dna> inactivation patterns can be used to determine whether proliferative disorders are clonal in origin .


Methylation of HpaII and Hha I sites near the polymorphic trinucleotide repeat of the human androgen receptor gene ( HUMARA ) has been shown to correlate with X-inactivation .

Methylation of <dna>HpaII and Hha I sites</dna> near the <dna>polymorphic trinucleotide repeat</dna> of the <dna>human androgen receptor gene</dna> ( <dna>HUMARA</dna> ) has been shown to correlate with X-inactivation .


In this study , we have used the polymerase chain reaction ( PCR ) with nested primers to analyze X-inactivation patterns of the HUMARA loci in purified eosinophils from female patients with eosinophilia .

In this study , we have used the polymerase chain reaction ( PCR ) with nested primers to analyze X-inactivation patterns of the <dna>HUMARA loci</dna> in <cell_type>purified eosinophils</cell_type> from female patients with eosinophilia .


Peripheral blood eosinophils were isolated by their autofluoresence using flow cytometric sorting .

<cell_type>Peripheral blood eosinophils</cell_type> were isolated by their autofluoresence using flow cytometric sorting .


Eosinophils purified from a female patient presenting with IHES were found to show a clonal pattern of X-inactivation .

<cell_type>Eosinophils</cell_type> purified from a female patient presenting with IHES were found to show a clonal pattern of X-inactivation .


Eosinophil-depleted leukocytes from this patient were polyclonal by HUMARA analysis , thus excluding skewedness of random X-inactivation .

<cell_type>Eosinophil-depleted leukocytes</cell_type> from this patient were polyclonal by <dna>HUMARA</dna> analysis , thus excluding skewedness of random X-inactivation .


After corticosteroid suppression of her blood eosinophilia , a clonal population of eosinophils could no longer be detected in purified eosinophils .

After corticosteroid suppression of her blood eosinophilia , a clonal population of <cell_type>eosinophils</cell_type> could no longer be detected in <cell_type>purified eosinophils</cell_type> .


In contrast , eosinophils purified from a patient with Churg-Strauss syndrome and from six patients with reactive eosinophilias attributed to allergy , parasitic infection , or drug reaction showed a polyclonal pattern of X-inactivation by HUMARA analysis .

In contrast , <cell_type>eosinophils</cell_type> purified from a patient with Churg-Strauss syndrome and from six patients with reactive eosinophilias attributed to allergy , parasitic infection , or drug reaction showed a polyclonal pattern of X-inactivation by <dna>HUMARA</dna> analysis .


The finding of clonal eosinophilia in a patient presenting with IHES indicates that such patients may have , in reality , a low-grade clonal disorder that can be distinguished from reactive eosinophilias by HUMARA analysis .

The finding of clonal eosinophilia in a patient presenting with IHES indicates that such patients may have , in reality , a low-grade clonal disorder that can be distinguished from reactive eosinophilias by <dna>HUMARA</dna> analysis .


Further , the method described can be used to monitor disease progression .


GA-binding protein factors , in concert with the coactivator CREB binding protein/p300 , control the induction of the interleukin 16 promoter in T lymphocytes .

<protein>GA-binding protein factors</protein> , in concert with the <protein>coactivator CREB binding protein/p300</protein> , control the induction of the <dna>interleukin 16 promoter</dna> in <cell_type>T lymphocytes</cell_type> .


Interleukin 16 ( IL-16 ) is a chemotactic cytokine that binds to the CD4 receptor and affects the activation of T cells and replication of HIV .

<protein>Interleukin 16</protein> ( <protein>IL-16</protein> ) is a <protein>chemotactic cytokine</protein> that binds to the <protein>CD4 receptor</protein> and affects the activation of <cell_type>T cells</cell_type> and replication of HIV .


It is expressed as a large 67-kDa precursor protein ( pro-IL-16 ) in lymphocytes , macrophages , and mast cells , as well as in airway epithelial cells from asthmatics after challenge with allergen .

It is expressed as a large <protein>67-kDa precursor protein</protein> ( <protein>pro-IL-16</protein> ) in <cell_type>lymphocytes</cell_type> , <cell_type>macrophages</cell_type> , and <cell_type>mast cells</cell_type> , as well as in <cell_type>airway epithelial cells</cell_type> from asthmatics after challenge with allergen .


This pro-IL-16 is subsequently processed to the mature cytokine of 13 kDa .

This <protein>pro-IL-16</protein> is subsequently processed to the mature cytokine of <protein>13 kDa</protein> .


To study the expression of IL-16 at the transcriptional level , we cloned the human chromosomal IL-16 gene and analyzed its promoter .

To study the expression of <protein>IL-16</protein> at the transcriptional level , we cloned the <dna>human chromosomal IL-16 gene</dna> and analyzed its promoter .


The human IL-16 gene consists of seven exons and six introns .

The <dna>human IL-16 gene</dna> consists of seven <dna>exons</dna> and six <dna>introns</dna> .


The 5 ' sequences up to nucleotide -120 of the human and murine IL-16 genes share > 84 % sequence homology and harbor promoter elements for constitutive and inducible transcription in T cells .

The <dna>5 ' sequences</dna> up to nucleotide -120 of the human and murine <protein>IL-16</protein> genes share > 84 % sequence homology and <dna>harbor promoter elements</dna> for constitutive and inducible transcription in <cell_type>T cells</cell_type> .


Although both promoters lack any TATA box , they contain two CAAT box-like motifs and three binding sites of GA-binding protein ( GABP ) transcription factors .

Although both promoters lack any <dna>TATA box</dna> , they contain two <dna>CAAT box-like motifs</dna> and three <dna>binding sites</dna> of <protein>GA-binding protein ( GABP ) transcription factors</protein> .


Two of these motifs are part of a highly conserved and inducible dyad symmetry element shown previously to control a remote IL-2 enhancer and the CD18 promoter .

Two of these motifs are part of a highly conserved and inducible <dna>dyad symmetry element</dna> shown previously to control a remote <dna>IL-2 enhancer</dna> and the <dna>CD18 promoter</dna> .


In concert with the coactivator CREB binding protein/p300 , which interacts with GABPalpha , the binding of GABPalpha and -beta to the dyad symmetry element controls the induction of IL-16 promoter in T cells .

In concert with the <protein>coactivator CREB binding protein/p300</protein> , which interacts with <protein>GABPalpha</protein> , the binding of <protein>GABPalpha</protein> and <protein>-beta</protein> to the <dna>dyad symmetry element</dna> controls the induction of <dna>IL-16 promoter</dna> in <cell_type>T cells</cell_type> .


Supplementing the data on the processing of pro-IL-16 , our results indicate the complexity of IL-16 expression , which is tightly controlled at the transcriptional and posttranslational levels in T lymphocytes .

Supplementing the data on the processing of <protein>pro-IL-16</protein> , our results indicate the complexity of <protein>IL-16</protein> expression , which is tightly controlled at the transcriptional and posttranslational levels in <cell_type>T lymphocytes</cell_type> .


Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene .

Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the <dna>vitamin D receptor gene</dna> .


The active metabolite of vitamin D , 1 , 25 dihydroxyvitamin D3 , is an important immunoregulatory hormone [ 1 ] .


Its effects are exerted by interaction with the vitamin D receptor , which is present on human monocytes and activated T and B lymphocytes .

Its effects are exerted by interaction with the <protein>vitamin D receptor</protein> , which is present on <cell_type>human monocytes</cell_type> and <cell_type>activated T and B lymphocytes</cell_type> .


Variation in the vitamin D receptor gene was typed in 2015 subjects from large case-control studies of three major infectious diseases : tuberculosis , malaria , and hepatitis B virus .

Variation in the <dna>vitamin D receptor gene</dna> was typed in 2015 subjects from large case-control studies of three major infectious diseases : tuberculosis , malaria , and hepatitis B virus .


Homozygotes for a polymorphism at codon 352 ( genotype tt ) were significantly underrepresented among those with tuberculosis ( chi2=6.22 , 1 df , P=.01 ) and persistent hepatitis B infection ( chi2=6.25 , 1 df , P=.01 ) but not in subjects with clinical malaria compared with the other genotypes .

Homozygotes for a polymorphism at <dna>codon 352</dna> ( genotype tt ) were significantly underrepresented among those with tuberculosis ( chi2=6.22 , 1 df , P=.01 ) and persistent hepatitis B infection ( chi2=6.25 , 1 df , P=.01 ) but not in subjects with clinical malaria compared with the other genotypes .


Therefore , this genetic variant , which predisposes to low bone mineral density in many populations , may confer resistance to certain infectious diseases .


Inhibition of NF-kappa B activation in vitro and in vivo : role of 26S proteasome .

Inhibition of <protein>NF-kappa B</protein> activation in vitro and in vivo : role of <protein>26S proteasome</protein> .


It is becoming increasingly apparent that NF-kappa B plays a critical role in regulating the inflammatory response .

It is becoming increasingly apparent that <protein>NF-kappa B</protein> plays a critical role in regulating the inflammatory response .


Data obtained from studies in our laboratories demonstrate that the proteasome plays an important role in the inflammatory cascade by regulating the activation of NF-kappa B .

Data obtained from studies in our laboratories demonstrate that the proteasome plays an important role in the inflammatory cascade by regulating the activation of <protein>NF-kappa B</protein> .


Indeed , the availability of selective and orally active proteasome inhibitors should prove useful in delineating the roles of the proteasome and NF-kappa B in other pathophysiological conditions such as cancer and heart disease .

Indeed , the availability of selective and orally active proteasome inhibitors should prove useful in delineating the roles of the proteasome and <protein>NF-kappa B</protein> in other pathophysiological conditions such as cancer and heart disease .


Tissue factor expression of human monocytes is suppressed by lysophosphatidylcholine .

Tissue factor expression of <cell_type>human monocytes</cell_type> is suppressed by lysophosphatidylcholine .


The expression of tissue factor ( TF ) , the principal initiator of coagulation , is increased during inflammation and atherosclerosis .

The expression of <protein>tissue factor</protein> ( <protein>TF</protein> ) , the principal initiator of coagulation , is increased during inflammation and atherosclerosis .


Both conditions are promoted by lysophosphatidylcholine ( lysoPC ) .


We observed in the present study that lysoPC ( 1 to 10 micromol/L ) dose-dependently reduced TF activity in human monocytes , as elicited by lipopolysaccharide ( LPS ) .

We observed in the present study that lysoPC ( 1 to 10 micromol/L ) dose-dependently reduced <protein>TF</protein> activity in <cell_type>human monocytes</cell_type> , as elicited by lipopolysaccharide ( LPS ) .


Lysophosphatidylethanolamine ( lysoPE ) and other lysophospholipids did not affect LPS-induced TF activity of human monocytes .

Lysophosphatidylethanolamine ( lysoPE ) and other lysophospholipids did not affect LPS-induced TF activity of <cell_type>human monocytes</cell_type> .


TF antigen expression as elicited by LPS was also lowered by lysoPC .


Phospholipid analyses indicated a selective increase in the lysoPC content of the monocytes after preincubation with the lysophospholipid .

Phospholipid analyses indicated a selective increase in the lysoPC content of the <cell_type>monocytes</cell_type> after preincubation with the lysophospholipid .


LysoPC inhibited the TF activity of Mono Mac-6 cells to a similar extent as in the monocytes .

LysoPC inhibited the TF activity of <cell_line>Mono Mac-6 cells</cell_line> to a similar extent as in the <cell_type>monocytes</cell_type> .


LPS binding to plasma membrane receptors and internalization of LPS into monocytes were not affected by lysoPC .

LPS binding to plasma membrane receptors and internalization of LPS into <cell_type>monocytes</cell_type> were not affected by lysoPC .


In contrast , LPS-mediated nuclear binding of nuclear factor-kappaB/Rel to a TF-specific kappaB site was inhibited by lysoPC .

In contrast , LPS-mediated nuclear binding of <protein>nuclear factor-kappaB/Rel</protein> to a <dna>TF-specific kappaB site</dna> was inhibited by lysoPC .


Induction of TF mRNA expression by LPS tended to be partially reduced by the lysophospholipid .

Induction of <rna>TF mRNA</rna> expression by LPS tended to be partially reduced by the lysophospholipid .


Preincubation with lysoPC increased monocytic cAMP levels .


Inhibition of adenylyl cyclase by pretreatment with 2'-deoxy-3'-adenosine monophosphate partially reversed the inhibition of TF activity promoted by lysoPC .

Inhibition of <protein>adenylyl cyclase</protein> by pretreatment with <protein>2'-deoxy-3'-adenosine monophosphate</protein> partially reversed the inhibition of TF activity promoted by lysoPC .


In conclusion , lysoPC markedly decreases LPS-mediated TF expression of human monocytes , the effect probably being mediated by both transcriptional and posttranscriptional mechanisms .

In conclusion , lysoPC markedly decreases LPS-mediated TF expression of <cell_type>human monocytes</cell_type> , the effect probably being mediated by both transcriptional and posttranscriptional mechanisms .


LysoPC may thus attenuate activation of coagulation during inflammation and atherosclerosis .


Regulation of fas-ligand expression during activation-induced cell death in T lymphocytes via nuclear factor kappaB .

Regulation of fas-ligand expression during activation-induced cell death in <cell_type>T lymphocytes</cell_type> via <protein>nuclear factor kappaB</protein> .


T cell receptor engagement activates transcription factors important for cytokine gene regulation .

T cell receptor engagement activates <protein>transcription factors</protein> important for <dna>cytokine gene</dna> regulation .


Additionally , this signaling pathway also leads to activation-induced apoptosis in T lymphocytes that is dependent on FasL transcription and expression .

Additionally , this signaling pathway also leads to activation-induced apoptosis in <cell_type>T lymphocytes</cell_type> that is dependent on FasL transcription and expression .


Here we demonstrate that nuclear factor kappaB ( NF-kappaB ) , which is involved in the transcriptional regulation of many cytokine genes expressed in activated lymphocytes , also plays a role in T cell activation-induced FasL expression .

Here we demonstrate that <protein>nuclear factor kappaB</protein> ( <protein>NF-kappaB</protein> ) , which is involved in the transcriptional regulation of many <dna>cytokine genes</dna> expressed in <cell_type>activated lymphocytes</cell_type> , also plays a role in T cell activation-induced <protein>FasL</protein> expression .


Inhibition of NF-kappaB activity in a T cell hybridoma leads to decreased FasL expression and apoptosis upon T cell receptor stimulation .

Inhibition of <protein>NF-kappaB</protein> activity in a <cell_line>T cell hybridoma</cell_line> leads to decreased <protein>FasL</protein> expression and apoptosis upon <protein>T cell receptor</protein> stimulation .


We identified the NF-kappaB site in the FasL promoter that contributes to such regulation .

We identified the <dna>NF-kappaB site</dna> in the <dna>FasL promoter</dna> that contributes to such regulation .


Co-expression of p65 ( Rel A ) with the FasL promoter enhanced its activity , and co-expression of IkappaB dramatically inhibited the inducible promoter activity .

Co-expression of <protein>p65 ( Rel A )</protein> with the <dna>FasL promoter</dna> enhanced its activity , and co-expression of <protein>IkappaB</protein> dramatically inhibited the <dna>inducible promoter</dna> activity .


In contrast , the transcription factor AP-1 is not required for activation-induced FasL promoter activity .

In contrast , the <protein>transcription factor AP-1</protein> is not required for activation-induced <protein>FasL</protein> promoter activity .


These results define a role for NF-kappaB in mediating FasL expression during T cell activation .

These results define a role for <protein>NF-kappaB</protein> in mediating <protein>FasL</protein> expression during T cell activation .


Promoter sequence , exon : intron structure , and synteny of genetic location show that a chicken cytokine with T-cell proliferative activity is IL2 and not IL15 .

<dna>Promoter sequence</dna> , exon : intron structure , and synteny of genetic location show that a <protein>chicken cytokine</protein> with T-cell proliferative activity is <protein>IL2</protein> and not <protein>IL15</protein> .


The gene encoding a chicken cytokine with T-cell proliferative activity was cloned , sequenced , and mapped .

The gene encoding a <protein>chicken cytokine</protein> with T-cell proliferative activity was cloned , sequenced , and mapped .


The results show that this cytokine is chicken IL2 and not IL15 .

The results show that this <protein>cytokine</protein> is chicken <protein>IL2</protein> and not <protein>IL15</protein> .


The exon : intron structure of chicken IL2 corresponds almost exactly to those of mammalian IL2s with the exceptions of exon 2 and introns 2 and 3 which are shorter .

The exon : intron structure of <protein>chicken IL2</protein> corresponds almost exactly to those of mammalian <protein>IL2s</protein> with the exceptions of <dna>exon 2</dna> and <dna>introns</dna> 2 and 3 which are shorter .


Chicken IL2 contains five repeats of the `` instability '' motif ATTTA in the 3'untranslated region in exon 4 .

Chicken <protein>IL2</protein> contains five repeats of the `` instability '' motif ATTTA in the <dna>3'untranslated region</dna> in <dna>exon 4</dna> .


It is a single-copy gene , with neither structural ( amino acid ) nor promoter sequence polymorphisms identified .

It is a <dna>single-copy gene</dna> , with neither structural ( amino acid ) nor promoter sequence polymorphisms identified .


Analysis of the predicted amino acid sequence suggests that overall protein structure is conserved , but the receptor binding sites are not .

Analysis of the predicted amino acid sequence suggests that overall <protein>protein structure</protein> is conserved , but the receptor binding sites are not .


A number of potential regulatory sequences similar to those found in mammals have been identified in the promoter .

A number of <dna>potential regulatory sequences</dna> similar to those found in mammals have been identified in the <dna>promoter</dna> .


These include ( 5'-3 ' ) a composite NF-AT/ `` AP-1 '' element , a CD28 response element , an AP-1 element , an NF-AT element , and the AP-1 part of an AP-1/octamer composite element .

These include ( 5'-3 ' ) a composite <dna>NF-AT/ `` AP-1 '' element</dna> , a <dna>CD28 response element</dna> , an <dna>AP-1 element</dna> , an <dna>NF-AT element</dna> , and the <dna>AP-1 part of an AP-1/octamer composite element</dna> .


The mammalian NF-kappaB and octamer binding sites seem to be absent , although there are alternative potential NF-kappaB and octamer-binding elements in the chicken IL2 promoter , in close proximity to their mammalian homologues .

The <protein>mammalian NF-kappaB</protein> and <dna>octamer binding sites</dna> seem to be absent , although there are alternative potential <protein>NF-kappaB</protein> and <dna>octamer-binding elements</dna> in the <dna>chicken IL2 promoter</dna> , in close proximity to their <dna>mammalian homologues</dna> .


Sequence comparisons also predict other potential transcription factor binding sites as yet undescribed in mammalian IL2 promoters .

Sequence comparisons also predict other potential transcription factor binding sites as yet undescribed in <dna>mammalian IL2 promoters</dna> .


A Taq I polymorphism was identified which enabled chicken IL2 to be mapped to chromosome 4 , linked to ANX5 , with synteny with mouse chromosome 3 and human chromosome 4 .

A <dna>Taq I polymorphism</dna> was identified which enabled chicken <protein>IL2</protein> to be mapped to <dna>chromosome 4</dna> , linked to <dna>ANX5</dna> , with synteny with <dna>mouse chromosome 3</dna> and <dna>human chromosome 4</dna> .


This is the first non-mammalian cytokine gene to be mapped .

This is the first <dna>non-mammalian cytokine gene</dna> to be mapped .


Endothelial production of MCP-1 : modulation by heparin and consequences for mononuclear cell activation .

Endothelial production of <protein>MCP-1</protein> : modulation by heparin and consequences for mononuclear cell activation .


Heparin is a polyanionic glycosaminoglycan ( GAG ) that can bind with high affinity to a range of cytokines including interferon-gamma ( IFN-gamma ) and members of the chemokine superfamily .

Heparin is a polyanionic glycosaminoglycan ( GAG ) that can bind with high affinity to a range of <protein>cytokines</protein> including <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) and members of the <protein>chemokine superfamily</protein> .


This GAG also possesses immunomodulatory activity in vivo and can antagonize the capacity of IFN-gamma to induce class II MHC antigen expression , and to up-regulate intercellular adhesion molecule-1 , by cultured endothelial cells .

This GAG also possesses immunomodulatory activity in vivo and can antagonize the capacity of <protein>IFN-gamma</protein> to induce <protein>class II MHC antigen</protein> expression , and to up-regulate <protein>intercellular adhesion molecule-1</protein> , by <cell_line>cultured endothelial cells</cell_line> .


Previous studies have shown that binding to cell-surface heparan sulphate is essential for optimal activity of IFN-gamma and that free heparin competitively inhibits this sequestration process .

Previous studies have shown that binding to cell-surface heparan sulphate is essential for optimal activity of <protein>IFN-gamma</protein> and that free heparin competitively inhibits this sequestration process .


The present study was performed to increase our understanding of the immunosuppressive activity of heparin by investigation of potential antagonism of the production and function of monocyte chemotactic peptide-1 ( MCP-1 ) , a chemokine important for mononuclear leucocyte recruitment across vascular endothelium .

The present study was performed to increase our understanding of the immunosuppressive activity of heparin by investigation of potential antagonism of the production and function of <protein>monocyte chemotactic peptide-1</protein> ( <protein>MCP-1</protein> ) , a <protein>chemokine</protein> important for mononuclear leucocyte recruitment across vascular endothelium .


It was found that mixture of heparin with IFN-gamma inhibited up-regulation of the signal transducer and activator of transcription protein , STAT-1 produced normally by treatment of endothelial cells with IFN-gamma .

It was found that mixture of heparin with <protein>IFN-gamma</protein> inhibited up-regulation of the signal transducer and activator of transcription protein , <protein>STAT-1</protein> produced normally by treatment of <cell_type>endothelial cells</cell_type> with <protein>IFN-gamma</protein> .


An inhibition of MCP-1 production was observed that was specifically caused by mixture of IFN-gamma with heparin-like , and therefore cytokine-binding , GAGs .

An inhibition of <protein>MCP-1</protein> production was observed that was specifically caused by mixture of <protein>IFN-gamma</protein> with heparin-like , and therefore cytokine-binding , GAGs .


It was also shown that mixture of heparin-like GAGs with MCP-1 inhibited the rapid tyrosine phosphorylation of phosphatidylinositol 3-kinase which is normally produced by treatment of mononuclear leucocytes with this chemokine .

It was also shown that mixture of heparin-like GAGs with <protein>MCP-1</protein> inhibited the rapid tyrosine phosphorylation of <protein>phosphatidylinositol 3-kinase</protein> which is normally produced by treatment of <cell_type>mononuclear leucocytes</cell_type> with this <protein>chemokine</protein> .


Blockade of this intracellular signalling event was associated with a reduction in the normal transendothelial migration response towards MCP-1 .

Blockade of this intracellular signalling event was associated with a reduction in the normal transendothelial migration response towards <protein>MCP-1</protein> .


Results from this study indicate that soluble , heparin-like GAGs can block IFN-gamma -dependent up-regulation of MCP-1 production by cultured endothelial cells , and can also antagonize the leucocyte-activating and migration-promoting properties of pre-existing MCP-1 .

Results from this study indicate that soluble , heparin-like GAGs can block <protein>IFN-gamma</protein> -dependent up-regulation of <protein>MCP-1</protein> production by <cell_line>cultured endothelial cells</cell_line> , and can also antagonize the leucocyte-activating and migration-promoting properties of pre-existing <protein>MCP-1</protein> .


These activities may contribute to the immunomodulatory properties of heparin .


[ Molecular-biologic aspects of interaction between nervous and immune systems ]


The problem of the neuro-immuno interactions on the level of the protein trans-factors , stimulating interleukin-2 ( IL-2 ) gene expression was discussed .

The problem of the neuro-immuno interactions on the level of the <protein>protein trans-factors</protein> , stimulating <dna>interleukin-2 ( IL-2 ) gene</dna> expression was discussed .


The physico-chemical and functional parameters of the low molecular nuclear proteins ( SP and BP- 14 , 18 , 19 kDs ) isolated from splenic and brain cells of immunized rats were studied .

The physico-chemical and functional parameters of the <protein>low molecular nuclear proteins</protein> ( <protein>SP</protein> and <protein>BP- 14 , 18 , 19 kDs</protein> ) isolated from <cell_type>splenic and brain cells</cell_type> of immunized rats were studied .


The binding of these proteins to the regulatory region of IL-2 gene in vitro and stimulation of the IL-2mRNA synthesis in splenic T-lymphocytes culture in normal conditions were shown .

The binding of these proteins to the regulatory region of <dna>IL-2 gene</dna> in vitro and stimulation of the <rna>IL-2mRNA</rna> synthesis in <cell_line>splenic T-lymphocytes culture</cell_line> in normal conditions were shown .


The protective effect of SP and BP on the IL-2mRNA synthesis in stressful conditions and by the T-cells treatment with the CsA was demonstrated .

The protective effect of <protein>SP</protein> and <protein>BP</protein> on the <rna>IL-2mRNA</rna> synthesis in stressful conditions and by the <cell_type>T-cells</cell_type> treatment with the CsA was demonstrated .


Interferon-alpha activates multiple STAT proteins and upregulates proliferation-associated IL-2Ralpha , c-myc , and pim-1 genes in human T cells .

<protein>Interferon-alpha</protein> activates multiple <protein>STAT proteins</protein> and upregulates proliferation-associated <protein>IL-2Ralpha</protein> , <dna>c-myc , and pim-1 genes</dna> in <cell_type>human T cells</cell_type> .


Interferon-alpha ( IFN-alpha ) is a pleiotropic cytokine that has antiviral , antiproliferative , and immunoregulatory functions .

<protein>Interferon-alpha</protein> ( <protein>IFN-alpha</protein> ) is a <protein>pleiotropic cytokine</protein> that has antiviral , antiproliferative , and <protein>immunoregulatory</protein> functions .


There is increasing evidence that IFN-alpha has an important role in T-cell biology .

There is increasing evidence that <protein>IFN-alpha</protein> has an important role in T-cell biology .


We have analyzed the expression of IL-2Ralpha , c-myc , and pim-1 genes in anti-CD3-activated human T lymphocytes .

We have analyzed the expression of <protein>IL-2Ralpha</protein> , <dna>c-myc</dna> , and <dna>pim-1 genes</dna> in <cell_type>anti-CD3-activated human T lymphocytes</cell_type> .


The induction of these genes is associated with interleukin-2 ( IL-2 ) -induced T-cell proliferation .

The induction of these genes is associated with <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) -induced T-cell proliferation .


Treatment of T lymphocytes with IFN-alpha , IL-2 , IL-12 , and IL-15 upregulated IL-2Ralpha , c-myc , and pim-1 gene expression .

Treatment of <cell_type>T lymphocytes</cell_type> with <protein>IFN-alpha</protein> , <protein>IL-2</protein> , <protein>IL-12</protein> , and <protein>IL-15</protein> upregulated <protein>IL-2Ralpha</protein> , <dna>c-myc</dna> , and <dna>pim-1 gene</dna> expression .


IFN-alpha also sensitized T cells to IL-2 -induced proliferation , further suggesting that IFN-alpha may be involved in the regulation of T-cell mitogenesis .

<protein>IFN-alpha</protein> also <cell_line>sensitized T cells</cell_line> to <protein>IL-2</protein> -induced proliferation , further suggesting that <protein>IFN-alpha</protein> may be involved in the regulation of T-cell mitogenesis .


When we analyzed the nature of STAT proteins capable of binding to IL-2Ralpha , pim-1 , and IRF-1 GAS elements after cytokine stimulation , we observed IFN-alpha -induced binding of STAT1 , STAT3 , and STAT4 , but not STAT5 to all of these elements .

When we analyzed the nature of <protein>STAT proteins</protein> capable of binding to <protein>IL-2Ralpha</protein> , <dna>pim-1 , and IRF-1 GAS elements</dna> after <protein>cytokine</protein> stimulation , we observed <protein>IFN-alpha</protein> -induced binding of <protein>STAT1</protein> , <protein>STAT3</protein> , and <protein>STAT4</protein> , but not <protein>STAT5</protein> to all of these elements .


Yet , IFN-alpha was able to activate binding of STAT5 to the high-affinity IFP53 GAS site .

Yet , <protein>IFN-alpha</protein> was able to activate binding of <protein>STAT5</protein> to the high-affinity IFP53 GAS site .