The IL-10R , together with reporter gene constructs containing different IL-6-responsive gene elements , reconstituted in hepatoma cells an induction of transcription by IL-10 that was comparable to that by IL-6 .

The <protein>IL-10R</protein> , together with reporter gene constructs containing different <dna>IL-6-responsive gene elements</dna> , reconstituted in <cell_type>hepatoma cells</cell_type> an induction of transcription by <protein>IL-10</protein> that was comparable to that by <protein>IL-6</protein> .


This regulation could not be appreciably modified by enhanced expression of STAT proteins .

This regulation could not be appreciably modified by enhanced expression of <protein>STAT proteins</protein> .


The similar actions of IL-10R and IL-6R on the induction of endogenous IL-6-responsive genes were demonstrated in hepatoma cells stably expressing the IL-10R .

The similar actions of <protein>IL-10R</protein> and <protein>IL-6R</protein> on the induction of endogenous <dna>IL-6-responsive genes</dna> were demonstrated in <cell_type>hepatoma cells</cell_type> stably expressing the <protein>IL-10R</protein> .


These receptor functions required the presence of the box 3 motifs , as shown by the analysis of the mouse IL-10R constructs containing progressively truncated cytoplasmic domains .

These receptor functions required the presence of the <protein>box 3 motifs</protein> , as shown by the analysis of the mouse <protein>IL-10R</protein> constructs containing <protein>progressively truncated cytoplasmic domains</protein> .


The data demonstrate that the IL-10R , unlike other members of the interferon receptor family , is highly effective in recruiting the signaling pathways of IL-6-type cytokine receptors .

The data demonstrate that the <protein>IL-10R</protein> , unlike other members of the interferon receptor family , is highly effective in recruiting the signaling pathways of <protein>IL-6-type cytokine receptors</protein> .


Induction of CIITA and modification of in vivo HLA-DR promoter occupancy in normal thymic epithelial cells treated with IFN-gamma : similarities and distinctions with respect to HLA-DR-constitutive B cells .

Induction of <protein>CIITA</protein> and modification of in vivo <dna>HLA-DR promoter</dna> occupancy in <cell_type>normal thymic epithelial cells</cell_type> treated with <protein>IFN-gamma</protein> : similarities and distinctions with respect to <cell_type>HLA-DR-constitutive B cells</cell_type> .


In this study , the IFN-gamma induction of MHC class II gene expression in primary cultures of thymic epithelial cells ( TEC ) was analyzed .

In this study , the <protein>IFN-gamma</protein> induction of <dna>MHC class II gene</dna> expression in primary cultures of <cell_line>thymic epithelial cells</cell_line> ( <cell_line>TEC</cell_line> ) was analyzed .


This cellular system offers the advantage that MHC class II induction is studied in a `` physiologic '' cell lineage that , as a result of this expression within the thymus , is thought to participate to the selection and maturation of the T cells .

This cellular system offers the advantage that <protein>MHC class II</protein> induction is studied in a <cell_type>`` physiologic '' cell lineage</cell_type> that , as a result of this expression within the thymus , is thought to participate to the selection and maturation of the <cell_type>T cells</cell_type> .


It was found that the MHC class II gene expression was associated with the de novo transcription of the gene encoding the CIITA trans-activator , a crucial MHC class II gene regulatory factor .

It was found that the <dna>MHC class II gene</dna> expression was associated with the de novo transcription of the gene encoding the <protein>CIITA trans-activator</protein> , a crucial <protein>MHC class II gene regulatory factor</protein> .


Furthermore , the anatomy of interaction between the MHC class II DRA promoter and corresponding binding factors was analyzed by in vivo DNAse I footprint .

Furthermore , the anatomy of interaction between the <dna>MHC class II DRA promoter</dna> and corresponding <protein>binding factors</protein> was analyzed by in vivo <protein>DNAse I</protein> footprint .


It was found that treatment with IFN-gamma induces changes in the occupancy of the DRA gene regulatory sequences by nuclear factors .

It was found that treatment with <protein>IFN-gamma</protein> induces changes in the occupancy of the <dna>DRA gene regulatory sequences</dna> by <protein>nuclear factors</protein> .


The resulting occupancy displays strong similarities with the one observed in the MHC class II-constitutive B cells , represented by both the Burkitt lymphoma line Raji and normal tonsil- derived B cells .

The resulting occupancy displays strong similarities with the one observed in the <cell_type>MHC class II-constitutive B cells</cell_type> , represented by both the <cell_line>Burkitt lymphoma line Raji</cell_line> and <cell_type>normal tonsil- derived B cells</cell_type> .


However , some peculiar differences were observed between the TEC , either IFN-gamma -induced or not , and the constitutive B cells .

However , some peculiar differences were observed between the <cell_line>TEC</cell_line> , either <protein>IFN-gamma</protein> -induced or not , and the constitutive <cell_line>B cells</cell_line> .


These results suggest that both common mechanisms , such as the one mediated by the CIITA trans-activator , and distinct tissue-specific constraints contribute to the transcriptional control of constitutive and IFN-gamma -induced MHC class II gene expression .

These results suggest that both common mechanisms , such as the one mediated by the <protein>CIITA trans-activator</protein> , and distinct tissue-specific constraints contribute to the transcriptional control of constitutive and <protein>IFN-gamma</protein> -induced <dna>MHC class II gene</dna> expression .


Inhibitory effect of E3330 , a novel quinone derivative able to suppress tumor necrosis factor-alpha generation , on activation of nuclear factor-kappa B .

Inhibitory effect of E3330 , a novel quinone derivative able to suppress <protein>tumor necrosis factor-alpha</protein> generation , on activation of <protein>nuclear factor-kappa B</protein> .


( 2E ) -3- [ 5- ( 2 , 3-Dimethoxy-6-methyl-1 , 4-benzoquinoyl ) ] -2-nonyl-2- propenoic acid ( E3330 ) , is a novel agent with hepatoprotective activity .


We report the effect of E3330 on transcriptional activation of tumor necrosis factor ( TNF ) -alpha gene and on nuclear factor ( NF ) -kappa B activation .

We report the effect of E3330 on transcriptional activation of <dna>tumor necrosis factor ( TNF ) -alpha gene</dna> and on <protein>nuclear factor ( NF ) -kappa B</protein> activation .


Nuclear run-on experiments showed that E3330 decreases transcriptional activation of TNF-alpha gene induced by lipopolysaccharide ( LPS ) stimulation in human peripheral monocytes .

Nuclear run-on experiments showed that E3330 decreases transcriptional activation of <dna>TNF-alpha gene</dna> induced by lipopolysaccharide ( LPS ) stimulation in <cell_type>human peripheral monocytes</cell_type> .


To investigate the inhibitory mechanisms , we constructed a secreted-type placental alkaline phosphatase ( PLAP ) reporter gene whose transcription is controlled by a 1.4-kb human TNF-alpha promoter .

To investigate the inhibitory mechanisms , we constructed a <dna>secreted-type placental alkaline phosphatase ( PLAP ) reporter gene</dna> whose transcription is controlled by a <dna>1.4-kb human TNF-alpha promoter</dna> .


A stable transformant of the PLAP reporter gene derived from human monocytic cell line showed very little activity on the promoter before stimulation , whereas LPS stimulation led to a dramatic increase in PLAP activity .

A stable transformant of the <dna>PLAP reporter gene</dna> derived from <cell_line>human monocytic cell line</cell_line> showed very little activity on the promoter before stimulation , whereas LPS stimulation led to a dramatic increase in <protein>PLAP</protein> activity .


E3330 inhibited this induced promoter activity in a dose-dependent manner .


There are four putative NF-kappa B binding sites ( kappa B-1 , kappa B-2 , kappa B-3 , kappa B-4 ) in human TNF-alpha promoter .

There are four putative <dna>NF-kappa B binding sites</dna> ( <dna>kappa B-1</dna> , <dna>kappa B-2</dna> , <dna>kappa B-3</dna> , <dna>kappa B-4</dna> ) in <dna>human TNF-alpha promoter</dna> .


By using mutated promoter-PLAP plasmids , we established that these NF-kappa B sites were necessary for induction of TNF-alpha transcription on stimulation with LPS .

By using <dna>mutated promoter-PLAP plasmids</dna> , we established that these <dna>NF-kappa B sites</dna> were necessary for induction of <protein>TNF-alpha</protein> transcription on stimulation with LPS .


A gel retardation experiment with synthetic double-stranded oligonucleotides showed that activated NF-kappa B consisting of p50/p65 heterodimer bound to all four putative NF-kappa B DNA probes , suggesting that all four putative NF-kappa B recognition sites play an important role in inducible TNF-alpha expression .

A gel retardation experiment with synthetic double-stranded oligonucleotides showed that activated <protein>NF-kappa B</protein> consisting of <protein>p50/p65 heterodimer</protein> bound to all four putative <dna>NF-kappa B DNA probes</dna> , suggesting that all four putative <dna>NF-kappa B recognition sites</dna> play an important role in inducible <protein>TNF-alpha</protein> expression .


E3330 decreased activated NF-kappa B in nuclei , suggesting that E3330 inhibits NF-kappa B activation and/or translocation of the nuclei .

E3330 decreased activated <protein>NF-kappa B</protein> in nuclei , suggesting that E3330 inhibits <protein>NF-kappa B</protein> activation and/or translocation of the nuclei .


Western blotting analysis with anti-I kappa B-alpha antibody indicated that E3330 inhibited degradation of I kappa B-alpha , which is an inhibitory protein of NF-kappa B , in LPS-stimulated monocytes .

Western blotting analysis with <protein>anti-I kappa B-alpha antibody</protein> indicated that E3330 inhibited degradation of <protein>I kappa B-alpha</protein> , which is an <protein>inhibitory protein</protein> of <protein>NF-kappa B</protein> , in <cell_line>LPS-stimulated monocytes</cell_line> .


E3330 may suppress the production of active oxygen species serving as common messengers to activate NF-kappa B .

E3330 may suppress the production of active oxygen species serving as common messengers to activate <protein>NF-kappa B</protein> .


C-terminal activating and inhibitory domains determine the transactivation potential of BSAP ( Pax-5 ) , Pax-2 and Pax-8 .

<protein>C-terminal activating and inhibitory domains</protein> determine the transactivation potential of <protein>BSAP</protein> ( <dna>Pax-5</dna> ) , <dna>Pax-2</dna> and <dna>Pax-8</dna> .


Pax-5 encodes the transcription factor BSAP which plays an essential role in early B cell development and midbrain patterning .

<dna>Pax-5</dna> encodes the <protein>transcription factor</protein> <protein>BSAP</protein> which plays an essential role in early B cell development and midbrain patterning .


In this study we have analysed the structural requirements for transcriptional activation by BSAP .

In this study we have analysed the structural requirements for transcriptional activation by <protein>BSAP</protein> .


In vitro mutagenesis and transient transfection experiments indicate that the C-terminal serine/threonine/proline-rich region of BSAP contains a potent transactivation domain of 55 amino acids which is active from promoter and enhancer positions .

In vitro mutagenesis and transient transfection experiments indicate that the <protein>C-terminal serine/threonine/proline-rich region</protein> of <protein>BSAP</protein> contains a potent <protein>transactivation domain</protein> of 55 amino acids which is active from <dna>promoter and enhancer positions</dna> .


This transactivation domain was found to be inactivated by a naturally occurring frameshift mutation in one PAX-5 allele of the acute lymphoblastic leukemia cell line REH .

This <protein>transactivation domain</protein> was found to be inactivated by a naturally occurring frameshift mutation in one <dna>PAX-5 allele</dna> of the <cell_line>acute lymphoblastic leukemia cell line REH</cell_line> .


The function of the transactivation domain is negatively regulated by adjacent sequences from the extreme C-terminus .

The function of the <protein>transactivation domain</protein> is negatively regulated by adjacent sequences from the <protein>extreme C-terminus</protein> .


The activating and inhibitory domains function together as an independent regulatory module in different cell types as shown by fusion to the GAL4 DNA binding domain .

The activating and inhibitory domains function together as an independent regulatory module in different cell types as shown by fusion to the <protein>GAL4 DNA binding domain</protein> .


The same arrangement of positively and negatively acting sequences has been conserved in the mammalian Pax-2 and Pax-8 , the zebrafish Pax-b as well as the sea urchin Pax-258 proteins .

The same arrangement of <dna>positively and negatively acting sequences</dna> has been conserved in the <dna>mammalian Pax-2</dna> and <dna>Pax-8</dna> , the <dna>zebrafish Pax-b</dna> as well as the <protein>sea urchin Pax-258 proteins</protein> .


These data demonstrate that the transcriptional competence of a subfamily of Pax proteins is determined by a C-terminal regulatory module composed of activating and inhibitory sequences .

These data demonstrate that the transcriptional competence of a subfamily of <protein>Pax proteins</protein> is determined by a <protein>C-terminal regulatory module</protein> composed of <dna>activating and inhibitory sequences</dna> .


Second messenger up-regulation of androgen receptor gene transcription is absent in androgen insensitive human prostatic carcinoma cell lines , PC-3 and DU-145 .

Second messenger up-regulation of <dna>androgen receptor gene</dna> transcription is absent in <cell_line>androgen insensitive human prostatic carcinoma cell lines</cell_line> , <cell_line>PC-3</cell_line> and <cell_line>DU-145</cell_line> .


A theoretical pathway of transcriptional regulation of the androgen receptor ( AR ) gene is via a cAMP response element ( CRE ) present in its promoter region ( -508 to -501 ) .

A theoretical pathway of transcriptional regulation of the <dna>androgen receptor ( AR ) gene</dna> is via a <dna>cAMP response element</dna> ( <dna>CRE</dna> ) present in its <dna>promoter region</dna> ( -508 to -501 ) .


After 20 h of stimulation with 8-bromo-cAMP , AR mRNA was upregulated in LNCaP but not in either PC-3 or DU-145 cell lines .

After 20 h of stimulation with 8-bromo-cAMP , <rna>AR mRNA</rna> was upregulated in <cell_line>LNCaP</cell_line> but not in either <cell_line>PC-3</cell_line> or <cell_line>DU-145 cell lines</cell_line> .


We have demonstrated that the level of CRE binding protein ( CREB ) was the same in all cell lines and that the putative AR-CRE forms specific and compatible protein interactions with CREB .

We have demonstrated that the level of <protein>CRE binding protein</protein> ( <protein>CREB</protein> ) was the same in all cell lines and that the putative <protein>AR-CRE</protein> forms specific and compatible protein interactions with <protein>CREB</protein> .


The ability to regulate AR gene transcription via the second messenger pathway is lost in the PC-3 and DU-145 cell lines .

The ability to regulate <dna>AR gene</dna> transcription via the second messenger pathway is lost in the <cell_line>PC-3 and DU-145 cell lines</cell_line> .


This may be an important primary mechanism of androgen insensitivity in prostate cancer .


Structural and functional characterization of the human CD36 gene promoter : identification of a proximal PEBP2/CBF site .

Structural and functional characterization of the <dna>human CD36 gene promoter</dna> : identification of a proximal <dna>PEBP2/CBF site</dna> .


CD36 is a cell surface glycoprotein composed of a single polypeptide chain , which interacts with thrombospondin , collagens type I and IV , oxidized low density lipoprotein , fatty acids , anionic phospholipids , and erythrocytes parasitized with Plasmodium falciparum .

<protein>CD36</protein> is a cell surface <protein>glycoprotein</protein> composed of a single polypeptide chain , which interacts with <protein>thrombospondin</protein> , <protein>collagens type I and IV</protein> , oxidized <protein>low density lipoprotein</protein> , fatty acids , anionic phospholipids , and <cell_type>erythrocytes</cell_type> parasitized with Plasmodium falciparum .


Its expression is restricted to a few cell types , including monocyte/macrophages .

Its expression is restricted to a few cell types , including <cell_type>monocyte/macrophages</cell_type> .


In these cells , CD36 is involved in phagocytosis of apoptotic cells , and foam cell formation by uptake of oxidized low density lipoprotein .

In these cells , <protein>CD36</protein> is involved in phagocytosis of <cell_type>apoptotic cells</cell_type> , and foam cell formation by uptake of <protein>oxidized low density lipoprotein</protein> .


To study the molecular mechanisms that control the transcription of the CD36 gene in monocytic cells we have isolated and analyzed the CD36 promoter .

To study the molecular mechanisms that control the transcription of the <protein>CD36</protein> gene in monocytic cells we have isolated and analyzed the <dna>CD36 promoter</dna> .


Transient expression experiments of 5'-deletion fragments of the CD36 promoter coupled to luciferase demonstrated that as few as 158 base pairs upstream from the transcription initiation site were sufficient to direct the monocyte-specific transcription of the reporter gene .

Transient expression experiments of <dna>5'-deletion fragments</dna> of the <dna>CD36 promoter</dna> coupled to <protein>luciferase</protein> demonstrated that as few as <dna>158 base pairs upstream</dna> from the <dna>transcription initiation site</dna> were sufficient to direct the monocyte-specific transcription of the <dna>reporter gene</dna> .


Within the above region , the fragment spanning nucleotides -158 to -90 was required for optimal transcription in monocytic cells .

Within the above region , the fragment spanning <dna>nucleotides -158 to -90</dna> was required for optimal transcription in <cell_type>monocytic cells</cell_type> .


Biochemical analysis of the region -158/-90 revealed a binding site for transcription factors of the polyomavirus enhancer-binding protein 2/core-binding factor ( PEBP2/CBF ) family at position -103 .

Biochemical analysis of the region <dna>-158/-90</dna> revealed a binding site for <protein>transcription factors</protein> of the <protein>polyomavirus enhancer-binding protein 2/core-binding factor ( PEBP2/CBF ) family</protein> at <dna>position -103</dna> .


Disruption of the PEBP2/CBF site markedly diminished the role of the PEBP2/CBF factors in the constitutive transcription of the CD36 gene .

Disruption of the <dna>PEBP2/CBF site</dna> markedly diminished the role of the <protein>PEBP2/CBF factors</protein> in the constitutive transcription of the <dna>CD36 gene</dna> .


The involvement of members of the PEBP2/CBF family in chromosome translocations associated with acute myeloid leukemia , and in the transcriptional regulation of the myeloid-specific genes encoding for myeloperoxidase , elastase , and the colony-stimulating factor receptor , highlights the relevance of the regulation of the CD36 gene promoter in monocytic cells by members of the PEBP2/CBF family .

The involvement of members of the <protein>PEBP2/CBF family</protein> in chromosome translocations associated with acute myeloid leukemia , and in the transcriptional regulation of the <dna>myeloid-specific genes</dna> encoding for <protein>myeloperoxidase</protein> , <protein>elastase</protein> , and the <protein>colony-stimulating factor receptor</protein> , highlights the relevance of the regulation of the <dna>CD36 gene promoter</dna> in <cell_type>monocytic cells</cell_type> by members of the <protein>PEBP2/CBF family</protein> .


HLA-DQB1 codon 57 is critical for peptide binding and recognition .

<dna>HLA-DQB1 codon 57</dna> is critical for peptide binding and recognition .


The association of specific HLA-DQ alleles with autoimmunity is correlated with discrete polymorphisms in the HLA-DQ sequence that are localized within sites suitable for peptide recognition .

The association of specific <dna>HLA-DQ alleles</dna> with autoimmunity is correlated with discrete polymorphisms in the <dna>HLA-DQ sequence</dna> that are localized within sites suitable for peptide recognition .


The polymorphism at residue 57 of the DQB1 polypeptide is of particular interest since it may play a major structural role in the formation of a salt bridge structure at one end of the peptide-binding cleft of the DQ molecules .

The polymorphism at residue 57 of the DQB1 polypeptide is of particular interest since it may play a major structural role in the formation of a <protein>salt bridge structure</protein> at one end of the <protein>peptide-binding cleft</protein> of the DQ molecules .


This polymorphism at residue 57 is a recurrent feature of HLA-DQ evolution , occurring in multiple distinct allelic families , which implies a functional selection for maintaining variation at this position in the class II molecule .

This polymorphism at residue 57 is a recurrent feature of HLA-DQ evolution , occurring in multiple distinct allelic families , which implies a functional selection for maintaining variation at this position in the <protein>class II molecule</protein> .


We directly tested the amino acid polymorphism at this site as a determinant for peptide binding and for antigen-specific T cell stimulation .


We found that a single Ala -- > Asp amino acid 57 substitution in an HLA-DQ3.2 molecule regulated binding of an HSV-2 VP-16-derived peptide .


A complementary single-residue substitution in the peptide abolished its binding to DQ3.2 and converted it to a peptide that can bind to DQ3.1 and DQ3.3 Asp-57-positive MHC molecules .

A complementary single-residue substitution in the peptide abolished its binding to DQ3.2 and converted it to a peptide that can bind to DQ3.1 and <protein>DQ3.3 Asp-57-positive MHC molecules</protein> .


These binding studies were paralleled by specific T cell recognition of the class II-peptide complex , in which the substituted peptide abolished T cell reactivity , which was directed to the DQ3.2-peptide complex , whereas the same T cell clone recognized the substituted peptide presented by DQ3.3 , a class II restriction element differing from DQ3.2 only at residue 57 .

These binding studies were paralleled by specific T cell recognition of the <protein>class II-peptide complex</protein> , in which the substituted peptide abolished T cell reactivity , which was directed to the <protein>DQ3.2-peptide complex</protein> , whereas the same <cell_line>T cell clone</cell_line> recognized the substituted peptide presented by DQ3.3 , a class II restriction element differing from DQ3.2 only at residue 57 .


This structural and functional complementarity for residue 57 and a specific peptide residue identifies this interaction as a key controlling determinant of restricted recognition in HLA-DQ-specific immune response .


Autocrine activation by interferon-gamma of STAT factors following T cell activation .

Autocrine activation by <protein>interferon-gamma</protein> of <protein>STAT factors</protein> following T cell activation .


The activation of T cells requires engagement of the T cell receptor/CD3 complex and co-stimulatory molecules , and results in the triggering of several signaling pathways which lead rapidly to the nuclear translocation of several transcription factors , such as nuclear factor ( NF ) -kappa B and NF-AT .

The activation of <cell_type>T cells</cell_type> requires engagement of the <protein>T cell receptor/CD3 complex</protein> and <protein>co-stimulatory molecules</protein> , and results in the triggering of several signaling pathways which lead rapidly to the nuclear translocation of several <protein>transcription factors</protein> , such as <protein>nuclear factor ( NF ) -kappa B</protein> and <protein>NF-AT</protein> .


A result of this activation process is the induction of a number of genes , including those encoding cytokines such as interleukin-2 , tumor necrosis factor-alpha , and interferon ( IFN ) -gamma which have important immunoregulatory effects .

A result of this activation process is the induction of a number of genes , including those encoding <protein>cytokines</protein> such as <protein>interleukin-2</protein> , <protein>tumor necrosis factor-alpha</protein> , and <protein>interferon ( IFN ) -gamma</protein> which have important <protein>immunoregulatory</protein> effects .


We report here that a DNA-binding factor containing STAT1 also becomes activated in human peripheral blood T lymphocytes or Jurkat cells , although not until 1-2 h after stimulation .

We report here that a <protein>DNA-binding factor</protein> containing <protein>STAT1</protein> also becomes activated in <cell_type>human peripheral blood T lymphocytes</cell_type> or <cell_line>Jurkat cells</cell_line> , although not until 1-2 h after stimulation .


Activation is delayed a further 1-2 hr when mononuclear cell cultures are stimulated by an antigen which requires processing .

Activation is delayed a further 1-2 hr when <cell_line>mononuclear cell cultures</cell_line> are stimulated by an antigen which requires processing .


Appearance of the STAT1 factor is significantly reduced in the presence of cyclosporin A , and blocked by cycloheximide , indicating that its activation is dependent upon a protein ( s ) synthesized in response to initial signaling events .

Appearance of the <protein>STAT1</protein> factor is significantly reduced in the presence of cyclosporin A , and blocked by cycloheximide , indicating that its activation is dependent upon a protein ( s ) synthesized in response to initial signaling events .


Neutralizing antiserum against IFN-gamma , but not other cytokines tested , blocked activation of the factor almost completely , and IFN-gamma was found in the culture supernatants of stimulated cells at levels at which recombinant IFN-gamma could activate the factor in naive cells .

Neutralizing antiserum against <protein>IFN-gamma</protein> , but not other <protein>cytokines</protein> tested , blocked activation of the factor almost completely , and <protein>IFN-gamma</protein> was found in the culture supernatants of <cell_line>stimulated cells</cell_line> at levels at which recombinant <protein>IFN-gamma</protein> could activate the factor in <cell_type>naive cells</cell_type> .


Therefore , a STAT1 transcription factor is activated by IFN-gamma synthesized and released upon stimulation of T lymphocyte populations .

Therefore , a <protein>STAT1</protein> <protein>transcription factor</protein> is activated by <protein>IFN-gamma</protein> synthesized and released upon stimulation of <cell_type>T lymphocyte populations</cell_type> .


While Jurkat cells both secrete and respond to IFN-gamma in an autocrine loop , it seems likely that the responding cells may differ from those synthesizing this cytokine in the mononuclear cell cultures in the light of the recent report that Th1 cells lack the IFN-gamma receptor chain necessary for activation of STAT1 ( Pernis , A. , Gupta , S. , Gollob , K.J. , Garfein , E. , Coffman , R.L. , Schindler , C. , and Rothman , P. , Science 1995. 269 : 245 ) .

While <cell_line>Jurkat cells</cell_line> both secrete and respond to <protein>IFN-gamma</protein> in an autocrine loop , it seems likely that the responding cells may differ from those synthesizing this <protein>cytokine</protein> in the <cell_line>mononuclear cell cultures</cell_line> in the light of the recent report that <cell_line>Th1 cells</cell_line> lack the <protein>IFN-gamma</protein> receptor chain necessary for activation of <protein>STAT1</protein> ( Pernis , A. , Gupta , S. , Gollob , K.J. , Garfein , E. , Coffman , R.L. , Schindler , C. , and Rothman , P. , Science 1995. 269 : 245 ) .


Absence of T-cell- and B-cell-specific transcription factors TCF-1 , GATA-3 , and BSAP in Hodgkin 's Reed-Sternberg cells .

Absence of <protein>T-cell- and B-cell-specific transcription factors</protein> <protein>TCF-1</protein> , <protein>GATA-3</protein> , and <protein>BSAP</protein> in <cell_line>Hodgkin 's Reed-Sternberg cells</cell_line> .


Based on the presence of T cell receptor-beta ( TcR-beta ) gene rearrangements in L428 and HDLM-1 cells , the expression of CD2 in HDLM-1 cells , and the presence of immunoglobulin heavy-chain ( IgH ) gene rearrangement in KM-H2 cells , some researchers have concluded that these long-term cell lines derived from patients with Hodgkin 's disease are lymphoid in nature .

Based on the presence of <dna>T cell receptor-beta ( TcR-beta ) gene rearrangements</dna> in <cell_line>L428 and HDLM-1 cells</cell_line> , the expression of <protein>CD2</protein> in <cell_line>HDLM-1 cells</cell_line> , and the presence of <dna>immunoglobulin heavy-chain ( IgH ) gene rearrangement</dna> in <cell_line>KM-H2 cells</cell_line> , some researchers have concluded that these <cell_line>long-term cell lines</cell_line> derived from patients with Hodgkin 's disease are lymphoid in nature .


The information obtained from these cell lines has also been used in arguments for a lymphoid origin of H-RS cells in tissue despite the frequent absence of lymphoid markers and Ig/TcR gene rearrangements in these cells .

The information obtained from these <cell_line>cell lines</cell_line> has also been used in arguments for a lymphoid origin of <cell_line>H-RS cells</cell_line> in tissue despite the frequent absence of <protein>lymphoid markers</protein> and <dna>Ig/TcR gene rearrangements</dna> in these cells .


We questioned whether one can use the limited expression of lymphoid markers or the limited gene rearrangement to conclude that H-RS cells have a lymphoid origin , because these markers may be aberrant in tumor cells .

We questioned whether one can use the limited expression of <protein>lymphoid markers</protein> or the limited gene rearrangement to conclude that <cell_line>H-RS cells</cell_line> have a lymphoid origin , because these markers may be aberrant in <cell_type>tumor cells</cell_type> .


In this study , we examined the expression of two T-cell-specific transcription factors ( TCF-1 and GATA-3 ) and one B-cell-specific transcription factor ( BSAP ) in cultured H-RS cells by using a gel mobility shift assay .

In this study , we examined the expression of two <protein>T-cell-specific transcription factors</protein> ( <protein>TCF-1</protein> and <protein>GATA-3</protein> ) and one <protein>B-cell-specific transcription factor</protein> ( <protein>BSAP</protein> ) in <cell_line>cultured H-RS cells</cell_line> by using a gel mobility shift assay .


The sensitivity and specificity of this assay for determination of cell lineage have been established in a large number of cultured human and murine cell lines .

The sensitivity and specificity of this assay for determination of <cell_line>cell lineage</cell_line> have been established in a large number of <cell_line>cultured human and murine cell lines</cell_line> .


All three types of H-RS cell lines were consistently negative for BSAP , TCF-1 , and GATA-3 .

All three types of <cell_line>H-RS cell lines</cell_line> were consistently negative for <protein>BSAP</protein> , <protein>TCF-1</protein> , and <protein>GATA-3</protein> .


The absence of GATA-3 was confirmed in H-RS cells in tissues by an in situ hybridization technique .

The absence of <protein>GATA-3</protein> was confirmed in <cell_line>H-RS cells</cell_line> in tissues by an in situ hybridization technique .


Virtually all B-cell lines , with the exception of some myeloma cell lines , are positive for BSAP , which is the transcription factor for promoters for several B-cell markers , including VpreB1 , lambda 5 , CD19 , and CD20 .

Virtually all <cell_line>B-cell lines</cell_line> , with the exception of some <cell_line>myeloma cell lines</cell_line> , are positive for <protein>BSAP</protein> , which is the <protein>transcription factor</protein> for <dna>promoters</dna> for several <protein>B-cell markers</protein> , including <protein>VpreB1</protein> , <protein>lambda 5</protein> , <protein>CD19</protein> , and <protein>CD20</protein> .


All T-cell lines tested were positive for TCF-1 and GATA-3 , which are the transcription factors for promoters for several T-cell-restricted markers , including CD2 , CD3 , TcR , and lck .

All <cell_line>T-cell lines</cell_line> tested were positive for <protein>TCF-1</protein> and <protein>GATA-3</protein> , which are the <protein>transcription factors</protein> for promoters for several <protein>T-cell-restricted markers</protein> , including <protein>CD2</protein> , <protein>CD3</protein> , <protein>TcR</protein> , and <protein>lck</protein> .


The absence of BSAP , TCF-1 , and GATA-3 clearly indicates an underlying difference between H-RS cells and lymphoid cells .

The absence of <protein>BSAP</protein> , <protein>TCF-1</protein> , and <protein>GATA-3</protein> clearly indicates an underlying difference between <cell_line>H-RS cells</cell_line> and <cell_type>lymphoid cells</cell_type> .


MEK1 and the extracellular signal-regulated kinases are required for the stimulation of IL-2 gene transcription in T cells .

<protein>MEK1</protein> and the <protein>extracellular signal-regulated kinases</protein> are required for the stimulation of <dna>IL-2 gene</dna> transcription in <cell_type>T cells</cell_type> .


TCR engagement stimulates the activation of the protein kinase Raf-1 .

<protein>TCR</protein> engagement stimulates the activation of the <protein>protein kinase</protein> <protein>Raf-1</protein> .


Active Raf-1 phosphorylates and activates the mitogen-activated protein ( MAP ) kinase/extracellular signal-regulated kinase kinase 1 ( MEK1 ) , which in turn phosphorylates and activates the MAP kinases/extracellular signal regulated kinases , ERK1 and ERK2 .

Active <protein>Raf-1</protein> phosphorylates and activates the <protein>mitogen-activated protein ( MAP ) kinase/extracellular signal-regulated kinase kinase 1</protein> ( <protein>MEK1</protein> ) , which in turn phosphorylates and activates the <protein>MAP kinases/extracellular signal regulated kinases</protein> , <protein>ERK1</protein> and <protein>ERK2</protein> .


Raf-1 activity promotes IL-2 production in activated T lymphocytes .

<protein>Raf-1</protein> activity promotes IL-2 production in activated <cell_type>T lymphocytes</cell_type> .


Therefore , we sought to determine whether MEK1 and ERK activities also stimulate IL-2 gene transcription .

Therefore , we sought to determine whether <protein>MEK1</protein> and <protein>ERK</protein> activities also stimulate <dna>IL-2 gene</dna> transcription .


Expression of constitutively active Raf-1 or MEK1 in Jurkat T cells enhanced the stimulation of IL-2 promoter -driven transcription stimulated by a calcium ionophore and PMA , and together with a calcium ionophore the expression of each protein was sufficient to stimulate NF-AT activity .

Expression of constitutively active <protein>Raf-1</protein> or <protein>MEK1</protein> in <cell_line>Jurkat T cells</cell_line> enhanced the stimulation of <dna>IL-2 promoter</dna> -driven transcription stimulated by a calcium ionophore and PMA , and together with a calcium ionophore the expression of each protein was sufficient to stimulate <protein>NF-AT</protein> activity .


Expression of MEK1-interfering mutants inhibited the stimulation of IL-2 promoter -driven transcription and blocked the ability of constitutively active Ras and Raf-1 to costimulate NF-AT activity with a calcium ionophore .

Expression of <protein>MEK1-interfering mutants</protein> inhibited the stimulation of <dna>IL-2 promoter</dna> -driven transcription and blocked the ability of constitutively active <protein>Ras</protein> and <protein>Raf-1</protein> to costimulate <protein>NF-AT</protein> activity with a calcium ionophore .


Expression of the MAP kinase-specific phosphatase , MKP-1 , which blocks ERK activation , inhibited IL-2 promoter and NF-AT -driven transcription stimulated by a calcium ionophore and PMA , and in addition , MKP-1 neutralized the transcriptional enhancement caused by active Raf-1 and MEK1 expression .

Expression of the <protein>MAP kinase-specific phosphatase</protein> , <protein>MKP-1</protein> , which blocks <protein>ERK</protein> activation , inhibited <dna>IL-2 promoter</dna> and <protein>NF-AT</protein> -driven transcription stimulated by a calcium ionophore and PMA , and in addition , <protein>MKP-1</protein> neutralized the transcriptional enhancement caused by active Raf-1 and MEK1 expression .


We conclude that the MAP kinase signal transduction pathway consisting of Raf-1 , MEK1 , and ERK1 and ERK2 functions in the stimulation IL-2 gene transcription in activated T lymphocytes .

We conclude that the <protein>MAP kinase</protein> signal transduction pathway consisting of <protein>Raf-1</protein> , <protein>MEK1</protein> , and <protein>ERK1</protein> and <protein>ERK2</protein> functions in the stimulation <dna>IL-2 gene</dna> transcription in activated <cell_type>T lymphocytes</cell_type> .


Multiple transcription factors are required for activation of human interleukin 9 gene in T cells .

Multiple <protein>transcription factors</protein> are required for activation of <dna>human interleukin 9 gene</dna> in <cell_type>T cells</cell_type> .


The genetic elements and regulatory mechanisms responsible for human interleukin 9 ( IL-9 ) gene expression in a human T cell leukemia virus type I-transformed human T cell line , C5MJ2 , were investigated .

The genetic elements and regulatory mechanisms responsible for <dna>human interleukin 9 ( IL-9 ) gene</dna> expression in a <cell_line>human T cell leukemia virus type I-transformed human T cell line</cell_line> , <cell_line>C5MJ2</cell_line> , were investigated .


We demonstrated that IL-9 gene expression is controlled , at least in part , by transcriptional activation .

We demonstrated that <dna>IL-9 gene</dna> expression is controlled , at least in part , by transcriptional activation .


Transient expression of the luciferase reporter gene linked to serially deleted sequences of the 5'-flanking region of the IL-9 gene has revealed several positive and negative regulatory elements involved in the basal and inducible expression of the IL-9 gene in C5MJ2 cells .

Transient expression of the <dna>luciferase reporter gene</dna> linked to serially deleted sequences of the <dna>5'-flanking region</dna> of the <dna>IL-9 gene</dna> has revealed several positive and <dna>negative regulatory elements</dna> involved in the basal and inducible expression of the <dna>IL-9 gene</dna> in <cell_line>C5MJ2 cells</cell_line> .


An AP-1 site at -146 to -140 was shown to be involved in the expression of the IL-9 gene .

An AP-1 site at -146 to -140 was shown to be involved in the expression of the <dna>IL-9 gene</dna> .


A proximal region between -46 and -80 was identified as the minimum sequence for the basal and inducible expression of the IL-9 gene in C5MJ2 cells .

A <dna>proximal region</dna> between <dna>-46 and -80</dna> was identified as the minimum sequence for the basal and inducible expression of the <dna>IL-9 gene</dna> in <cell_line>C5MJ2 cells</cell_line> .


Within this region , an NF-kappaB site at -59 to -50 and its adjacent 20-base pair upstream sequence were demonstrated to play a critical role for the IL-9 promoter activity .

Within this region , an <dna>NF-kappaB site</dna> at <dna>-59 to -50</dna> and its adjacent <dna>20-base pair upstream sequence</dna> were demonstrated to play a critical role for the <dna>IL-9 promoter</dna> activity .


DNA-protein binding studies indicated that NF-kappaB , c-Jun , and potentially novel proteins ( around 35 kDa ) can bind to this important sequence .

DNA-protein binding studies indicated that <protein>NF-kappaB</protein> , <protein>c-Jun</protein> , and potentially <protein>novel proteins</protein> ( around <protein>35 kDa</protein> ) can bind to this important sequence .


Mutations at different sites within this proximal promoter region abolished the promoter activity as well as the DNA binding .

Mutations at different sites within this <dna>proximal promoter region</dna> abolished the promoter activity as well as the DNA binding .


Taken together , these results suggest that the cooperation of different transcription factors is essential for IL-9 gene expression in T cells .

Taken together , these results suggest that the cooperation of different <protein>transcription factors</protein> is essential for <dna>IL-9 gene</dna> expression in <cell_type>T cells</cell_type> .


DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells .

DNA triplex formation selectively inhibits <dna>granulocyte-macrophage colony-stimulating factor gene</dna> expression in human T cells .


Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) is a hemopoietic growth factor that is expressed in activated T cells , fibroblasts , macrophages , and endothelial cells .

<protein>Granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) is a hemopoietic growth factor that is expressed in activated T cells , fibroblasts , macrophages , and endothelial cells .


Although GM-CSF does not appear to be essential for normal hemopoiesis , overexpression of GM-CSF has been implicated in the pathogenesis of some diseases such as myeloid leukemia and chronic inflammation .

Although <protein>GM-CSF</protein> does not appear to be essential for normal hemopoiesis , overexpression of GM-CSF has been implicated in the pathogenesis of some diseases such as myeloid leukemia and chronic inflammation .


An NF-kappaB /Rel binding site within the GM-CSF promoter , termed the kappaB element appears to be important for controlling expression in reporter gene assays in response to a number of stimuli in T cells .

An <protein>NF-kappaB</protein> /Rel binding site within the <dna>GM-CSF promoter</dna> , termed the kappaB element appears to be important for controlling expression in <dna>reporter gene</dna> assays in response to a number of stimuli in <cell_type>T cells</cell_type> .


We investigated oligonucleotide-directed triple helix formation across this regulatory sequence as a potential tool to inhibit GM-CSF gene transcription .

We investigated oligonucleotide-directed triple helix formation across this <dna>regulatory sequence</dna> as a potential tool to inhibit <protein>GM-CSF</protein> gene transcription .


A 15-base oligonucleotide , GM3 , was targeted to a purine-rich region in the GM-CSF proximal promoter , which overlaps the kappaB element .

A 15-base oligonucleotide , GM3 , was targeted to a <dna>purine-rich region</dna> in the <dna>GM-CSF proximal promoter</dna> , which overlaps the <dna>kappaB element</dna> .


Gel mobility shift assays and DNase I footprinting demonstrated that GM3 formed a sequence-specific collinear triplex with its double-stranded DNA target .

Gel mobility shift assays and <protein>DNase I</protein> footprinting demonstrated that GM3 formed a sequence-specific collinear triplex with its <dna>double-stranded DNA target</dna> .


Triplex formation by GM3 blocked recombinant and nuclear NF-kappaB proteins binding to the GM-CSF element .

Triplex formation by GM3 blocked <protein>recombinant and nuclear NF-kappaB proteins</protein> binding to the <dna>GM-CSF element</dna> .


GM3 also caused selective inhibition of the human T-cell lymphotrophic virus-1 Tax transactivator-induced luciferase activity from a reporter construct driven by the GM-CSF promoter in Jurkat T cells .

GM3 also caused selective inhibition of the <protein>human T-cell lymphotrophic virus-1 Tax</protein> transactivator-induced <protein>luciferase</protein> activity from a reporter construct driven by the <dna>GM-CSF promoter</dna> in <cell_line>Jurkat T cells</cell_line> .


Finally , GM3 greatly reduced the concentration of endogenous GM-CSF mRNA induced by different stimuli in Jurkat T cells but did not affect interleukin 3 mRNA levels in the same cells .

Finally , GM3 greatly reduced the concentration of endogenous <rna>GM-CSF mRNA</rna> induced by different stimuli in <cell_line>Jurkat T cells</cell_line> but did not affect <rna>interleukin 3 mRNA</rna> levels in the same cells .


We conclude that the kappaB element in the GM-CSF promoter plays a central role in the transcriptional activation of the endogenous GM-CSF gene .

We conclude that the <dna>kappaB element</dna> in the <dna>GM-CSF promoter</dna> plays a central role in the transcriptional activation of the endogenous <dna>GM-CSF gene</dna> .


Colinear triplex formation acts as a selective transcriptional repressor of the GM-CSF gene and may have potential therapeutic application in cases of undesirable overexpression of this protein .

Colinear triplex formation acts as a selective transcriptional repressor of the <dna>GM-CSF gene</dna> and may have potential therapeutic application in cases of undesirable overexpression of this protein .


Reversible differentiation of human monoblastic leukemia U937 cells by ML-9 , an inhibitor of myosin light chain kinase .

Reversible differentiation of <cell_line>human monoblastic leukemia U937 cells</cell_line> by ML-9 , an inhibitor of <protein>myosin light chain kinase</protein> .


Human monoblastic leukemia U937 cells are induced to differentiate into monocytes and macrophages by various agents .

<cell_line>Human monoblastic leukemia U937 cells</cell_line> are induced to differentiate into <cell_type>monocytes</cell_type> and <cell_type>macrophages</cell_type> by various agents .


We have shown that 1- ( 5-chloronaphthalene-1-sulfonyl ) -1H-hexahydro-1 , 4-diazepine hydrochloride ( ML-9 ) , an inhibitor of myosin light chain kinase , induces differentiation of monocytoid leukemia cell lines U937 and THP-1 but not of myeloblastic leukemic ML-1 cell or erythroleukemia K562 cells .

We have shown that 1- ( 5-chloronaphthalene-1-sulfonyl ) -1H-hexahydro-1 , 4-diazepine hydrochloride ( ML-9 ) , an inhibitor of <protein>myosin light chain kinase</protein> , induces differentiation of <cell_line>monocytoid leukemia cell lines</cell_line> <cell_line>U937</cell_line> and <cell_line>THP-1</cell_line> but not of <cell_line>myeloblastic leukemic ML-1 cell</cell_line> or <cell_line>erythroleukemia K562 cells</cell_line> .


In the present study , we further analyzed the effect of ML-9 in comparison with that of 1 alpha , 25-dihydroxyvitamin D3 ( VD3 ) a typical inducer of monocytic differentiation .


ML-9 induced nitroblue tetrazolium ( NBT ) -reducing activity of U937 cell more rapidly than VD3 : This differentiation marker was induced significantly after incubation with ML-9 and VD3 for 4 hours and 1 day , respectively .

ML-9 induced nitroblue tetrazolium ( NBT ) -reducing activity of <cell_line>U937 cell</cell_line> more rapidly than VD3 : This differentiation marker was induced significantly after incubation with ML-9 and VD3 for 4 hours and 1 day , respectively .


ML-9 also induced alpha-naphthyl acetate esterase ( ANAE ) activity , another monocytic differentiation marker , more rapidly than VD3 .

ML-9 also induced <protein>alpha-naphthyl acetate esterase</protein> ( <protein>ANAE</protein> ) activity , another monocytic differentiation marker , more rapidly than VD3 .


The maximum levels of these markers induced by ML-9 were comparable to those induced by VD3 , but after removal of ML-9 from the medium by washing the cells , the expressions of theses markers decreased within 4 hours and reached basal levels in 1 day , indicating that ML-9 's induction of expression of differentiation-associated phenotypes was reversible .


The growth inhibition of U937 cells by ML-9 was also reversible .

The growth inhibition of <cell_line>U937 cells</cell_line> by ML-9 was also reversible .


Similar effects were observed in another line of human monoblastic cells , THP-1 .

Similar effects were observed in another line of <cell_line>human monoblastic cells</cell_line> , <cell_line>THP-1</cell_line> .


ML-9 had little or no effect on the morphology of U937 cells but increased the expression of monocyte-macrophage lineage-associated surface antigen , CD14 , to some extent .

ML-9 had little or no effect on the morphology of <cell_line>U937 cells</cell_line> but increased the expression of <protein>monocyte-macrophage lineage-associated surface antigen</protein> , <protein>CD14</protein> , to some extent .


Irreversible terminal differentiation induced by VD3 is associated with down regulation of the expression of c-myc and upregulation of the expression of c-fos and c-jun , but ML-9 did not affect the expression of these oncogenes appreciably .


ML-9-induced differentiation was also reversible when the cells were cultured with cultured with ML-9 plus an anti-cancer drug such as 1-beta-D-arabino-furanosylcytosine or daunomycin .


it became irreversible , however , upon simultaneous treatment with dexamethasone and transforming growth factor-beta 1 ( TGF-beta 1 ) , which did not induce differentiation of U937 cells but caused growth arrest of the cells in the G0/G1 phase of the cell cycle .

it became irreversible , however , upon simultaneous treatment with dexamethasone and <protein>transforming growth factor-beta 1</protein> ( <protein>TGF-beta 1</protein> ) , which did not induce differentiation of <cell_line>U937 cells</cell_line> but caused growth arrest of the cells in the G0/G1 phase of the cell cycle .


These results suggest that ML-9 should be useful for studying the mechanisms of monocytic differentiation .


Modulation of endogenous IL-1 beta and IL-1 receptor antagonist results in opposing effects on HIV expression in chronically infected monocytic cells .

Modulation of endogenous <protein>IL-1 beta</protein> and <protein>IL-1 receptor</protein> antagonist results in opposing effects on HIV expression in <cell_line>chronically infected monocytic cells</cell_line> .


A proportion of HIV-infected individuals experience episodes of localized or systemic bacterial infections caused by Gram-negative bacteria .


Many of the clinical side effects of these infections are associated with the production of proinflammatory cytokines , which are induced primarily by LPS , a constituent of the bacterial cell wall of Gram-negative bacteria .

Many of the clinical side effects of these infections are associated with the production of <protein>proinflammatory cytokines</protein> , which are induced primarily by LPS , a constituent of the bacterial cell wall of Gram-negative bacteria .


The present study examines the mechanisms involved in LPS-mediated induction of HIV expression in U1 cells , a promonocytic cell line chronically infected with HIV .

The present study examines the mechanisms involved in LPS-mediated induction of HIV expression in <cell_line>U1 cells</cell_line> , a <cell_line>promonocytic cell line</cell_line> chronically infected with HIV .


Stimulation of U1 cells by LPS alone induced minimal levels of HIV expression , which was significantly enhanced by granulocyte-macrophage colony-stimulating factor ( GM-CSF ) .

Stimulation of <cell_line>U1 cells</cell_line> by LPS alone induced minimal levels of HIV expression , which was significantly enhanced by <protein>granulocyte-macrophage colony-stimulating factor</protein> ( <protein>GM-CSF</protein> ) .


Costimulation of U1 cells with LPS plus GM-CSF resulted in the accumulation of steady-state levels of HIV RNA ; however , only a weak induction of HIV long terminal repeat -driven transcription , which was not associated with the activation of the cellular transcription factor nuclear factor-kappa B , was noted .

Costimulation of <cell_line>U1 cells</cell_line> with LPS plus <protein>GM-CSF</protein> resulted in the accumulation of steady-state levels of <rna>HIV RNA</rna> ; however , only a weak induction of <dna>HIV long terminal repeat</dna> -driven transcription , which was not associated with the activation of the <protein>cellular transcription factor</protein> <protein>nuclear factor-kappa B</protein> , was noted .


Costimulation of cells with LPS plus GM-CSF induced the production of proinflammatory cytokines , IL-8 , IL-1 beta and IL-6 , but not TNF-alpha .

Costimulation of cells with LPS plus <protein>GM-CSF</protein> induced the production of <protein>proinflammatory cytokines</protein> , <protein>IL-8</protein> , <protein>IL-1 beta</protein> and <protein>IL-6</protein> , but not <protein>TNF-alpha</protein> .


IL-1 receptor antagonist ( ra ) inhibited LPS enhancement of HIV expression in GM-CSF-stimulated cells , suggesting that endogenous IL-1 was involved in LPS-mediated viral production .

<protein>IL-1 receptor</protein> antagonist ( ra ) inhibited LPS enhancement of HIV expression in <cell_line>GM-CSF-stimulated cells</cell_line> , suggesting that <protein>endogenous IL-1</protein> was involved in LPS-mediated viral production .


In this regard , anti-inflammatory cytokines inhibited LPS plus GM-CSF -stimulated HIV expression , and this effect closely correlated with inhibition of IL-1 beta release and , in particular , with up-regulation of endogenous IL-1ra production .

In this regard , <protein>anti-inflammatory cytokines</protein> inhibited LPS plus <protein>GM-CSF</protein> -stimulated HIV expression , and this effect closely correlated with inhibition of <protein>IL-1 beta</protein> release and , in particular , with up-regulation of endogenous IL-1ra production .


Thus , the balance between an endogenously produced viral inducer ( IL-1 beta ) and an inhibitor ( IL-1ra ) may represent an important pathway leading to modulation of HIV expression from monocytic cells .

Thus , the balance between an <protein>endogenously produced viral inducer</protein> ( <protein>IL-1 beta</protein> ) and an inhibitor ( <protein>IL-1ra</protein> ) may represent an important pathway leading to modulation of HIV expression from <cell_type>monocytic cells</cell_type> .


Herpesvirus saimiri immortalized gamma delta T cell line activated by IL-12 .

<cell_line>Herpesvirus saimiri immortalized gamma delta T cell line</cell_line> activated by <protein>IL-12</protein> .


IL-12 is a novel heterodimeric cytokine important for the regulation and differentiation of lymphocytes and NK cells .

<protein>IL-12</protein> is a novel <protein>heterodimeric cytokine</protein> important for the regulation and differentiation of lymphocytes and NK cells .


Like other cytokines , IL-12 mediates its biologic activity through high-affinity receptors expressed on responsive cells .

Like other cytokines , <protein>IL-12</protein> mediates its biologic activity through high-affinity receptors expressed on <cell_type>responsive cells</cell_type> .


To date , a large number of receptors for IL-12 have been found only on PBMC following activation with PHA or IL-2 .

To date , a large number of receptors for <protein>IL-12</protein> have been found only on <cell_type>PBMC</cell_type> following activation with <protein>PHA</protein> or <protein>IL-2</protein> .


To gain further knowledge of the IL-12R complex and the IL-12 signal transduction pathway in cytotoxic T cells , we studied a number of human T cell lines that had been transformed to permanent growth with Herpesvirus saimiri , an oncogenic virus of nonhuman primates .

To gain further knowledge of the <protein>IL-12R complex</protein> and the <protein>IL-12</protein> signal transduction pathway in <cell_type>cytotoxic T cells</cell_type> , we studied a number of <cell_line>human T cell lines</cell_line> that had been transformed to permanent growth with Herpesvirus saimiri , an oncogenic virus of nonhuman primates .


This paper reports the expression of IL-12R on a human gamma delta T cell line that responds to IL-12 with enhanced cytolytic activity and increased expression of cytolytic effector molecules granzyme B and perforin .

This paper reports the expression of <protein>IL-12R</protein> on a <cell_line>human gamma delta T cell line</cell_line> that responds to <protein>IL-12</protein> with enhanced cytolytic activity and increased expression of <protein>cytolytic effector molecules</protein> <protein>granzyme B</protein> and <protein>perforin</protein> .


Using these T cells as a model of IL-12 signal transduction , we confirmed that these events involve members of the Janus kinase family of nonreceptor tyrosine kinases JAK2 , TYK2 , and signal transducer and activator of transcription 4 .

Using these <cell_type>T cells</cell_type> as a model of <protein>IL-12</protein> signal transduction , we confirmed that these events involve members of the <protein>Janus kinase family</protein> of <protein>nonreceptor tyrosine kinases</protein> <protein>JAK2</protein> , <protein>TYK2</protein> , and <protein>signal transducer and activator of transcription 4</protein> .


Regulation of gene expression at early stages of B-cell and T-cell differentiation .


The expression of distinct sets of genes at different stages of B-lymphocyte and T-lymphocyte differentiation is controlled at the level of transcription .


A number of recent studies have described interactions between transcription factors in lymphocytes that provide new insights into mechanisms regulating gene expression .

A number of recent studies have described interactions between <protein>transcription factors</protein> in lymphocytes that provide new insights into mechanisms regulating gene expression .


These mechanisms include the assembly of higher order nucleoprotein complexes and other protein-protein interactions that enhance the functional specificity of transcriptional regulators in lymphocytes .

These mechanisms include the assembly of <protein>higher order nucleoprotein complexes</protein> and other protein-protein interactions that enhance the functional specificity of <protein>transcriptional regulators</protein> in lymphocytes .


Identification of a human LIM-Hox gene , hLH-2 , aberrantly expressed in chronic myelogenous leukaemia and located on 9q33-34.1 .

Identification of a <dna>human LIM-Hox gene</dna> , <dna>hLH-2</dna> , aberrantly expressed in chronic myelogenous leukaemia and located on <dna>9q33-34.1</dna> .


We describe the isolation of human LH-2 , a putative transcription factor containing two cysteine-rich regions ( LIM domains ) and a homeobox ( Hox ) DNA-binding domain .

We describe the isolation of <protein>human LH-2</protein> , a <protein>putative transcription factor</protein> containing two <protein>cysteine-rich regions</protein> ( <protein>LIM domains</protein> ) and a <protein>homeobox ( Hox ) DNA-binding domain</protein> .


High levels of hLH-2 expression were observed in all cases of chronic myelogenous leukaemia ( CML ) tested , regardless of disease status .

High levels of <dna>hLH-2</dna> expression were observed in all cases of chronic myelogenous leukaemia ( CML ) tested , regardless of disease status .


hLH-2 was mapped to chromosome 9Q33-34.1 , in the same region as the reciprocal translocation that creates the BCR-ABL chimera of the Philadelphia chromosome ( Ph ' ) , the hallmark of CML ; hLH-2 was retained on the derivative 9 chromosome and is therefore centromeric of c-ABL .

<dna>hLH-2</dna> was mapped to <dna>chromosome 9Q33-34.1</dna> , in the same region as the reciprocal translocation that creates the <protein>BCR-ABL chimera</protein> of the Philadelphia chromosome ( Ph ' ) , the hallmark of CML ; <dna>hLH-2</dna> was retained on the <dna>derivative 9 chromosome</dna> and is therefore centromeric of <dna>c-ABL</dna> .


The proximity of hLH-2 to the breakpoint on chromosome 9 raises the possibility of cis-activation by the t ( 9 ; 22 ) ( q34 ; q11 ) translocation .

The proximity of <dna>hLH-2</dna> to the breakpoint on <dna>chromosome 9</dna> raises the possibility of cis-activation by the <dna>t ( 9 ; 22 ) ( q34 ; q11 ) translocation</dna> .


In addition to finding hLH-2 expression in all cases of CML , expression was observed in lymphoid malignancies and myeloid cell lines , but not in primary cases of acute myelogenous leukaemia .

In addition to finding <dna>hLH-2</dna> expression in all cases of CML , expression was observed in lymphoid malignancies and <cell_line>myeloid cell lines</cell_line> , but not in primary cases of acute myelogenous leukaemia .


The role of hLH-2 in the development or progression of leukaemia is not known .

The role of <dna>hLH-2</dna> in the development or progression of leukaemia is not known .


However , hLH-2 may prove useful as a marker of CML for monitoring residual disease .

However , <dna>hLH-2</dna> may prove useful as a marker of CML for monitoring residual disease .


Lymphoid cell resistance to glucocorticoids in HIV infection .


In humans infected with the HIV-1 virus there may be a disproportionate severity of signs and symptoms of illness compared to the fraction of CD4+ infected T-lymphoid cells .

In humans infected with the HIV-1 virus there may be a disproportionate severity of signs and symptoms of illness compared to the fraction of <cell_line>CD4+ infected T-lymphoid cells</cell_line> .


In part , this may be due to altered intercellular signalling systems and intracellular signal transduction .


Glucocorticoids are well known for their effects on the vitality and function of lymphoid cells .

Glucocorticoids are well known for their effects on the vitality and function of <cell_type>lymphoid cells</cell_type> .


Patients with HIV infections often show elevated circulating levels of cortisol , suggesting some misfunction in the regulatory systems that maintain the levels of this critical hormone .


At the cellular level , it is known that both acute HIV infection and glucocorticoids can cause apoptotic cell death in thymic lymphocytes .

At the cellular level , it is known that both acute HIV infection and glucocorticoids can cause apoptotic cell death in <cell_type>thymic lymphocytes</cell_type> .


However , chronically HIV-infected cells appear to be resistant to glucocorticoid-evoked cell death .

However , <cell_type>chronically HIV-infected cells</cell_type> appear to be resistant to glucocorticoid-evoked cell death .


Glucocorticoid receptor -ligand binding studies on patients ' cells have shown reduced affinity between the receptor binding sites and test steroids .

<protein>Glucocorticoid receptor</protein> -ligand binding studies on patients ' cells have shown reduced affinity between the <protein>receptor binding sites</protein> and test steroids .


In vitro , chronically HIV-infected cells of the lymphoid CEM line displayed resistance to glucocorticoid-induced apoptosis .

In vitro , <cell_line>chronically HIV-infected cells</cell_line> of the <cell_line>lymphoid CEM line</cell_line> displayed resistance to glucocorticoid-induced apoptosis .


These cells showed reduced numbers of binding sites with little alteration in apparent affinity between ligand and receptor .

These cells showed reduced numbers of <protein>binding sites</protein> with little alteration in apparent affinity between ligand and receptor .


Thus it appears that there may often be malfunction of the normal glucocorticoid response in HIV-infected cells probably due to altered interactions between the glucocorticoid receptor and its hormone .

Thus it appears that there may often be malfunction of the normal glucocorticoid response in <cell_type>HIV-infected cells</cell_type> probably due to altered interactions between the <protein>glucocorticoid receptor</protein> and its hormone .


Such alterations may have clinical consequences , including the possibility of a relatively longer life span of infected CD4+ T-lymphocytes , as well as systemic effects of chronically elevated cortisol level .

Such alterations may have clinical consequences , including the possibility of a relatively longer life span of <cell_type>infected CD4+ T-lymphocytes</cell_type> , as well as systemic effects of chronically elevated cortisol level .


Abundant expression of erythroid transcription factor P45 NF-E2 mRNA in human peripheral granurocytes .

Abundant expression of <rna>erythroid transcription factor P45 NF-E2 mRNA</rna> in <cell_type>human peripheral granurocytes</cell_type> .


Transcription factor NF-E2 is crucial for regulation of erythroid-specific gene expression .

<protein>Transcription factor NF-E2</protein> is crucial for regulation of erythroid-specific gene expression .


p45 subunit of NF-E2 contains a basic-leucine zipper domain and dimerizes with the small Maf family protein to form functional NF-E2 complex .

<protein>p45 subunit</protein> of <protein>NF-E2</protein> contains a <protein>basic-leucine zipper domain</protein> and dimerizes with the <protein>small Maf family protein</protein> to form functional <protein>NF-E2 complex</protein> .


While p45 expression was shown to be restricted to erythroid cells , megakaryocytes and mast cells in hematopoietic lineage , we found in this study that p45 mRNA is abundantly transcribed in the granulocyte fraction of human peripheral blood cells .

While <protein>p45</protein> expression was shown to be restricted to <cell_type>erythroid cells</cell_type> , <cell_type>megakaryocytes</cell_type> and <cell_type>mast cells</cell_type> in hematopoietic lineage , we found in this study that <rna>p45 mRNA</rna> is abundantly transcribed in the <cell_type>granulocyte fraction</cell_type> of <cell_type>human peripheral blood cells</cell_type> .


As neutrophils occupy approximately 92 % of the cells in granulocyte fraction of human peripheral blood cells .

As <cell_type>neutrophils</cell_type> occupy approximately 92 % of the cells in <cell_type>granulocyte fraction</cell_type> of <cell_type>human peripheral blood cells</cell_type> .


As neutrophils occupy approximately 92 % of the cells in this fraction , the cells expressing p45 is most likely to be neutrophils .

As <cell_type>neutrophils</cell_type> occupy approximately 92 % of the cells in this fraction , the cells expressing <protein>p45</protein> is most likely to be <cell_type>neutrophils</cell_type> .


p45 mRNA is also expressed in HL-60 promyelocytes , albeit the expression level is much lower than that of the granulocyte fraction .

<rna>p45 mRNA</rna> is also expressed in <cell_line>HL-60 promyelocytes</cell_line> , albeit the expression level is much lower than that of the <cell_type>granulocyte fraction</cell_type> .


HL-60 cells were found to express mafK mRNA , indicating the presence of genuine NF-E2 complex in the cells .

<cell_line>HL-60 cells</cell_line> were found to express <rna>mafK mRNA</rna> , indicating the presence of genuine <protein>NF-E2 complex</protein> in the cells .


Although p45 mRNA is transcribed from two different promoters , aNF-E2 promoter and fNF-E2 promoter , in erythroid and megakaryocytic lineage cells , p45 mRNA is transcribed only from aNF-E2 promoter .

Although <rna>p45 mRNA</rna> is transcribed from two different promoters , <dna>aNF-E2 promoter</dna> and <dna>fNF-E2 promoter</dna> , in <cell_type>erythroid and megakaryocytic lineage cells</cell_type> , <rna>p45 mRNA</rna> is transcribed only from <dna>aNF-E2 promoter</dna> .


The expression of p45 megakaryocytic lineage cells , p45 mRNA is transcribed only from aNF-E2 promoter .

The expression of <protein>p45</protein> <cell_type>megakaryocytic lineage cells</cell_type> , <rna>p45 mRNA</rna> is transcribed only from <dna>aNF-E2 promoter</dna> .


The expression of p45 mRNA in the neutrophils declined rapidly after transfer of the cells to in vitro culture and G-CSF could not sustain the expression from the down-regulation , suggesting the E2 may also participate in the regulation of neutrophil-specific gene expression .

The expression of <rna>p45 mRNA</rna> in the <cell_type>neutrophils</cell_type> declined rapidly after transfer of the cells to in vitro culture and <protein>G-CSF</protein> could not sustain the expression from the down-regulation , suggesting the <protein>E2</protein> may also participate in the regulation of neutrophil-specific gene expression .


Expression of c-fos and c-jun proteins and AP-1 binding activity during cell cycle progression of HL60 cells and phytohemagglutinin-stimulated lymphocytes .

Expression of <protein>c-fos and c-jun proteins</protein> and <protein>AP-1</protein> binding activity during cell cycle progression of <cell_line>HL60 cells</cell_line> and <cell_line>phytohemagglutinin-stimulated lymphocytes</cell_line> .


The protein products of the c-fos ( p62c-fos ) and c-jun ( p39c-jun ) genes are members of the AP-1 transcription factor family and are thought to play important roles in the regulation of gene expression during the cell cycle .

The protein products of the <dna>c-fos</dna> ( <protein>p62c-fos</protein> ) and <dna>c-jun</dna> ( <protein>p39c-jun</protein> ) genes are members of the <protein>AP-1 transcription factor family</protein> and are thought to play important roles in the regulation of gene expression during the cell cycle .


Most studies on the expression of these proteins in relation to the cell cycle have been performed at the mRNA level , and therefore do not give direct information about the presence of the proteins during the cell cycle .


We have used Western blotting to investigate the presence of these proteins during the cell cycles of two different cellular systems : a continuously growing myeloid leukemic cell line , HL60 , and normal cells stimulated into cycle , phyto- hemagglutinin ( PHA ) -stimulated normal human peripheral blood lymphocytes ( PBL ) .

We have used Western blotting to investigate the presence of these proteins during the cell cycles of two different <cell_line>cellular systems</cell_line> : a <cell_line>continuously growing myeloid leukemic cell line</cell_line> , <cell_line>HL60</cell_line> , and <cell_type>normal cells</cell_type> stimulated into cycle , <cell_line>phyto- hemagglutinin ( PHA ) -stimulated normal human peripheral blood lymphocytes</cell_line> ( <cell_type>PBL</cell_type> ) .


The binding activity of transcription factor AP-1 , which consists of dimers of Fos and Jun family proteins , was also studied using a gel shift assay .

The binding activity of transcription factor <protein>AP-1</protein> , which consists of dimers of <protein>Fos and Jun family proteins</protein> , was also studied using a gel shift assay .


We found nuclear p62c-fos , p39c-jun , and AP-1 binding activity throughout the cell cycle both in HL60 cells and in PHA-stimulated PBL , and we postulate that these proteins are required throughout the cell cycle and not transiently in the G0 to G1 transition as previous mRNA studies have indicated .

We found nuclear <protein>p62c-fos</protein> , <protein>p39c-jun</protein> , and <protein>AP-1</protein> binding activity throughout the cell cycle both in <cell_line>HL60 cells</cell_line> and in <cell_line>PHA-stimulated PBL</cell_line> , and we postulate that these proteins are required throughout the cell cycle and not transiently in the G0 to G1 transition as previous mRNA studies have indicated .


We demonstrated an uncoupling of AP-1 binding activity from p62c-fos , and p39c-jun AP-1 activity was expressed more strongly in the G1- and G2/M-phase enriched samples than in the S-phase enriched samples of HL60 cells , while levels of nuclear p62c-fos and p39c-jun were constant .

We demonstrated an uncoupling of <protein>AP-1</protein> binding activity from <protein>p62c-fos</protein> , and <protein>p39c-jun</protein> <protein>AP-1</protein> activity was expressed more strongly in the G1- and G2/M-phase enriched samples than in the S-phase enriched samples of <cell_line>HL60 cells</cell_line> , while levels of <protein>nuclear p62c-fos and p39c-jun</protein> were constant .


Nuclei of unstimulated PBL from different donors expressed p62c-fos and p39c-jun , but AP-1 was not detected in the majority of samples .

Nuclei of <cell_type>unstimulated PBL</cell_type> from different donors expressed <protein>p62c-fos</protein> and <protein>p39c-jun</protein> , but <protein>AP-1</protein> was not detected in the majority of samples .


Following PHA stimulation of PBL , the increase in AP-1 activity was delayed with respect to the augmentation of p39c-jun expression .

Following <protein>PHA</protein> stimulation of <cell_type>PBL</cell_type> , the increase in <protein>AP-1</protein> activity was delayed with respect to the augmentation of <protein>p39c-jun</protein> expression .


We also observed that cytoplasmic p62c-fos and p39c-jun were present in HL60 cells and PHA-stimulated PBL .

We also observed that <protein>cytoplasmic p62c-fos and p39c-jun</protein> were present in <cell_line>HL60 cells</cell_line> and <cell_line>PHA-stimulated PBL</cell_line> .


However , no cytoplasmic p62c-fos was detected in unstimulated PBL , although in some cases cytoplasmic p39c-jun was detected , suggesting that subcellular compartmentalization of these proteins may occur under certain circumstances .

However , no <protein>cytoplasmic p62c-fos</protein> was detected in <cell_type>unstimulated PBL</cell_type> , although in some cases <protein>cytoplasmic p39c-jun</protein> was detected , suggesting that subcellular compartmentalization of these <protein>proteins</protein> may occur under certain circumstances .


Octamer binding factors and their coactivator can activate the murine PU.1 ( spi-1 ) promoter .

<protein>Octamer binding factors</protein> and their <protein>coactivator</protein> can activate the <dna>murine PU.1 ( spi-1 ) promoter</dna> .


PU.1 ( spi-1 ) , a member of the Ets transcription factor family , is predominantly expressed in myeloid and B cells , activates many B cell and myeloid genes , and is critical for development of both of these lineages .

<protein>PU.1</protein> ( <protein>spi-1</protein> ) , a member of the <protein>Ets transcription factor family</protein> , is predominantly expressed in <cell_type>myeloid and B cells</cell_type> , activates many <dna>B cell and myeloid genes</dna> , and is critical for development of both of these lineages .


Our previous studies ( Chen , H.M. , Ray-Gallet , D. , Zhang , P. , Hetherington , C.J. , Gonzalez , D.A. , Zhang , D.-E. , Moreau-Gachelin , F. , and Tenen , D.G. ( 1995 ) Oncogene 11 , 1549-1560 ) demonstrate that the PU.1 promoter directs cell type-specific reporter gene expression in myeloid cell lines , and that PU.1 activates its own promoter in an autoregulatory loop .

Our previous studies ( Chen , H.M. , Ray-Gallet , D. , Zhang , P. , Hetherington , C.J. , Gonzalez , D.A. , Zhang , D.-E. , Moreau-Gachelin , F. , and Tenen , D.G. ( 1995 ) Oncogene 11 , 1549-1560 ) demonstrate that the <dna>PU.1 promoter</dna> directs <dna>cell type-specific reporter gene</dna> expression in myeloid cell lines , and that <protein>PU.1</protein> activates its own promoter in an autoregulatory loop .


Here we show that the murine PU.1 promoter is also specifically and highly functional in B cell lines as well .

Here we show that the <dna>murine PU.1 promoter</dna> is also specifically and highly functional in <cell_line>B cell lines</cell_line> as well .


Oct-1 and Oct-2 can bind specifically to a site at base pair -55 in vitro , and this site is specifically protected in B cells in vivo .

<protein>Oct-1</protein> and <protein>Oct-2</protein> can bind specifically to a site at base pair -55 in vitro , and this site is specifically protected in <cell_type>B cells</cell_type> in vivo .


We also demonstrate that two other sites contribute to promoter activity in B cells ; an Sp1 binding site adjacent to the octamer site , and the PU.1 autoregulatory site .

We also demonstrate that two other sites contribute to promoter activity in <cell_type>B cells</cell_type> ; an <dna>Sp1 binding site</dna> adjacent to the <dna>octamer site</dna> , and the <dna>PU.1 autoregulatory site</dna> .


Finally , we show that the B cell coactivator OBF-1/Bob1/OCA-B is only expressed in B cells and not in myeloid cells , and that OBF-1/Bob1/OCA-B can transactivate the PU.1 promoter in HeLa and myeloid cells .

Finally , we show that the B cell <protein>coactivator</protein> <protein>OBF-1/Bob1/OCA-B</protein> is only expressed in <cell_type>B cells</cell_type> and not in <cell_type>myeloid cells</cell_type> , and that <protein>OBF-1/Bob1/OCA-B</protein> can transactivate the <dna>PU.1 promoter</dna> in <cell_line>HeLa</cell_line> and <cell_type>myeloid cells</cell_type> .


This B cell restricted coactivator may be responsible for the B cell specific expression of PU.1 mediated by the octamer site .

This <protein>B cell restricted coactivator</protein> may be responsible for the B cell specific expression of <protein>PU.1</protein> mediated by the <dna>octamer site</dna> .


Inhibition of p105 processing by NF-kappaB proteins in transiently transfected cells .

Inhibition of <protein>p105</protein> processing by <protein>NF-kappaB proteins</protein> in <cell_line>transiently transfected cells</cell_line> .


Regulation of the transcription factor NF-kappaB involves proteasome-mediated processing of the NF-kappaB1 p105 precursor protein , which generates the p50 subunit of NF-kappaB .

Regulation of the transcription factor <protein>NF-kappaB</protein> involves proteasome-mediated processing of the <protein>NF-kappaB1 p105 precursor protein</protein> , which generates the <protein>p50 subunit</protein> of <protein>NF-kappaB</protein> .


The processing of p105 occurs constitutively in vivo but can be markedly enhanced by various cellular activation agents , although the underlying regulatory mechanism is not yet clear .

The processing of <protein>p105</protein> occurs constitutively in vivo but can be markedly enhanced by various cellular activation agents , although the underlying regulatory mechanism is not yet clear .


In the present study , we demonstrate that signal-mediated induction of p105 processing in human T cells is associated with de novo synthesis of this precursor protein .

In the present study , we demonstrate that signal-mediated induction of <protein>p105</protein> processing in <cell_type>human T cells</cell_type> is associated with de novo synthesis of this <protein>precursor protein</protein> .


Transient transfection studies performed in COS7 cells revealed that the newly synthesized p105 protein appears to be more rapidly processed compared to its accumulated form that is already associated with the processed product p50 .

Transient transfection studies performed in <cell_line>COS7 cells</cell_line> revealed that the newly synthesized <protein>p105</protein> protein appears to be more rapidly processed compared to its accumulated form that is already associated with the processed product <protein>p50</protein> .


Interestingly , the processing rate of p105 is markedly inhibited in cells co-transfected with p50 or other NF-kappaB subunits , including RelA and c-Rel , that physically interact with p105 .

Interestingly , the processing rate of <protein>p105</protein> is markedly inhibited in cells co-transfected with <protein>p50</protein> or other <protein>NF-kappaB subunits</protein> , including <protein>RelA</protein> and <protein>c-Rel</protein> , that physically interact with <protein>p105</protein> .


These findings suggest that the processing of p105 is subject to negative regulation by the various NF-kappaB subunits .

These findings suggest that the processing of <protein>p105</protein> is subject to negative regulation by the various <protein>NF-kappaB subunits</protein> .


We further demonstrate that p105 undergoes degradation in lipopolysaccharide-stimulated human monocytic cells .

We further demonstrate that <protein>p105</protein> undergoes degradation in <cell_line>lipopolysaccharide-stimulated human monocytic cells</cell_line> .


However , the inducible degradation of p105 is not coupled with the generation of p50 .

However , the inducible degradation of <protein>p105</protein> is not coupled with the generation of <protein>p50</protein> .


Together , these studies demonstrate that the processing and inducible degradation of p105 are differentially regulated .

Together , these studies demonstrate that the processing and inducible degradation of <protein>p105</protein> are differentially regulated .


Identification of an inducible regulator of c-myb expression during T-cell activation .

Identification of an <protein>inducible regulator</protein> of <dna>c-myb</dna> expression during <cell_type>T-cell</cell_type> activation .


Resting T cells express very low levels of c-Myb protein .

<cell_type>Resting T cells</cell_type> express very low levels of <protein>c-Myb protein</protein> .


During T-cell activation , c-myb expression is induced and much of the increase in expression occurs at the transcriptional level .

During T-cell activation , <dna>c-myb</dna> expression is induced and much of the increase in expression occurs at the transcriptional level .


We identified a region of the c-myb 5 ' flanking sequence that increased c-myb expression during T-cell activation .

We identified a region of the <dna>c-myb 5 ' flanking sequence</dna> that increased <dna>c-myb</dna> expression during T-cell activation .


In vivo footprinting by ligation-mediated PCR was performed to correlate in vivo protein binding with functional activity .


A protein footprint was visible over this region of the c-myb 5 ' flanking sequence in activated T cells but not in unactivated T cells .

A protein footprint was visible over this region of the <dna>c-myb 5 ' flanking sequence</dna> in <cell_type>activated T cells</cell_type> but not in <cell_type>unactivated T cells</cell_type> .


An electrophoretic mobility shift assay ( EMSA ) with nuclear extract from activated T cells and an oligonucleotide of this binding site demonstrated a new protein-DNA complex , referred to as CMAT for c-myb in activated T cells ; this complex was not present in unactivated T cells .

An electrophoretic mobility shift assay ( EMSA ) with nuclear extract from <cell_type>activated T cells</cell_type> and an oligonucleotide of this binding site demonstrated a new <protein>protein-DNA complex</protein> , referred to as <protein>CMAT</protein> for <protein>c-myb in activated T cells</protein> ; this complex was not present in <cell_type>unactivated T cells</cell_type> .


Because the binding site showed some sequence similarity with the nuclear factor of activated T cells ( NFAT ) binding site , we compared the kinetics of induction of the two binding complexes and the molecular masses of the two proteins .

Because the <dna>binding site</dna> showed some sequence similarity with the <dna>nuclear factor of activated T cells ( NFAT ) binding site</dna> , we compared the kinetics of induction of the two binding complexes and the molecular masses of the two proteins .


Studies of the kinetics of induction showed that the NFAT EMSA binding complex appeared earlier than the CMAT complex .

Studies of the kinetics of induction showed that the <protein>NFAT EMSA binding complex</protein> appeared earlier than the <protein>CMAT complex</protein> .


The NFAT protein migrated more slowly in a sodium dodecyl sulfate-polyacrylamide gel than the CMAT protein did .

The <protein>NFAT</protein> protein migrated more slowly in a sodium dodecyl sulfate-polyacrylamide gel than the <protein>CMAT protein</protein> did .


In addition , an antibody against NFAT did not cross-react with the CMAT protein .

In addition , an antibody against <protein>NFAT</protein> did not cross-react with the <protein>CMAT protein</protein> .


The appearance of the CMAT binding complex was inhibited by both cyclosporin A and rapamycin .

The appearance of the <protein>CMAT binding complex</protein> was inhibited by both cyclosporin A and rapamycin .


The CMAT protein appears to be a novel inducible protein involved in the regulation of c-myb expression during T-cell activation .

The <protein>CMAT</protein> protein appears to be a novel inducible protein involved in the regulation of <dna>c-myb</dna> expression during T-cell activation .


CNI-1493 inhibits monocyte/macrophage tumor necrosis factor by suppression of translation efficiency .

CNI-1493 inhibits <protein>monocyte/macrophage tumor necrosis factor</protein> by suppression of translation efficiency .


Tumor necrosis factor ( TNF ) mediates a wide variety of disease states including septic shock , acute and chronic inflammation , and cachexia .

<protein>Tumor necrosis factor</protein> ( <protein>TNF</protein> ) mediates a wide variety of disease states including septic shock , acute and chronic inflammation , and cachexia .


Recently , a multivalent guanylhydrazone ( CNI-1493 ) developed as an inhibitor of macrophage activation was shown to suppress TNF production and protect against tissue inflammation and endotoxin lethality [ Bianchi , M. , Ulrich , P. , Bloom , O. , Meistrell , M. , Zimmerman , G.A. , Schmidtmayerova , H. , Bukrinsky , M. , Donnelley , T. , Bucala , R. , Sherry , B. , Manogue , K.R. , Tortolani , A.J. , Cerami , A. & Tracey , K.J. ( 1995 ) Mol.Med.1 , 254-266 , and Bianchi , M. , Bloom , O. , Raabe , T. , Cohen , P. S. , Chesney , J. , Sherry , B. , Schmidtmayerova , H. , Zhang , X. , Bukrinsky , M. , Ulrich , P. , Cerami , A. & Tracey , J. ( 1996 ) J.Exp.Med. , in press ] .

Recently , a multivalent guanylhydrazone ( CNI-1493 ) developed as an inhibitor of macrophage activation was shown to suppress <protein>TNF</protein> production and protect against tissue inflammation and endotoxin lethality [ Bianchi , M. , Ulrich , P. , Bloom , O. , Meistrell , M. , Zimmerman , G.A. , Schmidtmayerova , H. , Bukrinsky , M. , Donnelley , T. , Bucala , R. , Sherry , B. , Manogue , K.R. , Tortolani , A.J. , Cerami , A. & Tracey , K.J. ( 1995 ) Mol.Med.1 , 254-266 , and Bianchi , M. , Bloom , O. , Raabe , T. , Cohen , P. S. , Chesney , J. , Sherry , B. , Schmidtmayerova , H. , Zhang , X. , Bukrinsky , M. , Ulrich , P. , Cerami , A. & Tracey , J. ( 1996 ) J.Exp.Med. , in press ] .


We have now elucidated the mechanism by which CNI-1493 inhibits macrophage TNF synthesis and show here that it acts through suppression of TNF translation efficiency .

We have now elucidated the mechanism by which CNI-1493 inhibits macrophage <protein>TNF</protein> synthesis and show here that it acts through suppression of <protein>TNF</protein> translation efficiency .


CNI-1493 blocked neither the lipopolysaccharide ( LPS ) -induced increases in the expression of TNF mRNA nor the translocation of nuclear factor NF-kappa B to the nucleus in macrophages activated by 15 min of LPS stimulation , indicating that CNI-1493 does not interfere with early NF-kappa B -mediated transcriptional regulation of TNF .

CNI-1493 blocked neither the lipopolysaccharide ( LPS ) -induced increases in the expression of <rna>TNF mRNA</rna> nor the translocation of <protein>nuclear factor NF-kappa B</protein> to the nucleus in <cell_type>macrophages</cell_type> activated by 15 min of LPS stimulation , indicating that CNI-1493 does not interfere with early <protein>NF-kappa B</protein> -mediated transcriptional regulation of <protein>TNF</protein> .


However , synthesis of the 26-kDa membrane form of TNF was effectively blocked by CNI-1493 .

However , synthesis of the <protein>26-kDa membrane form</protein> of <protein>TNF</protein> was effectively blocked by CNI-1493 .


Further evidence for the translational suppression of TNF is given by experiments using chloram-phenicol acetyltransferase ( CAT ) constructs containing elements of the TNF gene that are involved in TNF translational regulation .

Further evidence for the translational suppression of <protein>TNF</protein> is given by experiments using <dna>chloram-phenicol acetyltransferase ( CAT ) constructs</dna> containing elements of the <dna>TNF gene</dna> that are involved in <protein>TNF</protein> translational regulation .


Both the 5 ' and 3 ' untranslated regions of the TNF gene were required to elicit maximal translational suppression by CNI-1493 .

Both the <dna>5 ' and 3 ' untranslated regions</dna> of the <dna>TNF gene</dna> were required to elicit maximal translational suppression by CNI-1493 .


Identification of the molecular target through which CNI- 1493 inhibits TNF translation should provide insight into the regulation of macrophage activation and mechanisms of inflammation .

Identification of the molecular target through which CNI- 1493 inhibits <protein>TNF</protein> translation should provide insight into the regulation of macrophage activation and mechanisms of inflammation .


Soluble tumor necrosis factor receptors inhibit phorbol myristate acetate and cytokine-induced HIV-1 expression chronically infected U1 cells .

<protein>Soluble tumor necrosis factor receptors</protein> inhibit phorbol myristate acetate and cytokine-induced HIV-1 expression chronically <cell_type>infected U1 cells</cell_type> .


Recombinant human tumor necrosis factor ( TNF ) binding protein-1 ( r-h TBP-1 ) and recombinant human soluble dimeric TNF receptor ( rhu TNFR : Fc ) were used to determine the relative contributions of TNF to phorbol myristate acetate ( PMA ) and cytokine-induced human immunodeficiency virus type 1 ( HIV-1 ) replication in chronically infected cell lines .

<protein>Recombinant human tumor necrosis factor ( TNF ) binding protein-1</protein> ( <protein>r-h TBP-1</protein> ) and <protein>recombinant human soluble dimeric TNF receptor</protein> ( <protein>rhu TNFR : Fc</protein> ) were used to determine the relative contributions of <protein>TNF</protein> to phorbol myristate acetate ( PMA ) and cytokine-induced human immunodeficiency virus type 1 ( HIV-1 ) replication in chronically infected cell lines .


Treatment of HIV-1-infected promonocytic U1 cells with r-h-TBP-1 or rhu TNFR : Fc reduced PMA-induced HIV-1 p24 antigen production in a concentration-dependent manner , with a maximal inhibition of approximately 90 % .

Treatment of <cell_type>HIV-1-infected promonocytic U1 cells</cell_type> with <protein>r-h-TBP-1</protein> or <protein>rhu TNFR : Fc</protein> reduced PMA-induced <protein>HIV-1 p24 antigen</protein> production in a concentration-dependent manner , with a maximal inhibition of approximately 90 % .


Maximal inhibition of p24 antigen production in T-lymphocytic ACH-2 cells was 47 % with r-hTBP-1 and 42 % with rhu TNFR : Fc .

Maximal inhibition of <protein>p24 antigen</protein> production in <cell_line>T-lymphocytic ACH-2 cells</cell_line> was 47 % with <protein>r-hTBP-1</protein> and 42 % with <protein>rhu TNFR : Fc</protein> .


r-hTBP-1 and rhu TNFR : Fc also decreased p24 antigen synthesized by U1 cells in response to other stimuli , including phytohemagglutinin ( PHA ) -induced supernatant , granulocyte-macrophage colony-stimulating factor , interleukin-6 , and TNF .

<protein>r-hTBP-1</protein> and <protein>rhu TNFR : Fc</protein> also decreased <protein>p24 antigen</protein> synthesized by <cell_line>U1 cells</cell_line> in response to other stimuli , including <protein>phytohemagglutinin ( PHA ) -induced supernatant</protein> , <protein>granulocyte-macrophage colony-stimulating factor</protein> , <protein>interleukin-6</protein> , and <protein>TNF</protein> .


Addition of r-hTBP-1 to U1 cells during the last 4 h of a 24 h incubation with PMA still inhibited p24 antigen production by 15 % .

Addition of <protein>r-hTBP-1</protein> to <cell_line>U1 cells</cell_line> during the last 4 h of a 24 h incubation with PMA still inhibited <protein>p24 antigen</protein> production by 15 % .


U1 cells stimulated with 10 ( -7 ) M PMA released approximately 1 ng/ml endogenous TBP-1 with an initial peak observed at 1 h and a second peak at 24 h after PMA stimulation .

<cell_line>U1 cells</cell_line> stimulated with 10 ( -7 ) M PMA released approximately 1 ng/ml <protein>endogenous TBP-1</protein> with an initial peak observed at 1 h and a second peak at 24 h after PMA stimulation .


r-hTBP-1 also partially reversed inhibition of U1 cellular proliferation caused by PMA .

<protein>r-hTBP-1</protein> also partially reversed inhibition of U1 cellular proliferation caused by PMA .


Both r-hTBP-1 and rhu TNFR : Fc blocked PMA induction of nuclear factor ( NK ) - kappa B DNA-binding activity in U1 cells in association with decreases in HIV-1 replication .

Both <protein>r-hTBP-1</protein> and <protein>rhu TNFR : Fc</protein> blocked PMA induction of <protein>nuclear factor ( NK ) - kappa B</protein> DNA-binding activity in <cell_line>U1 cells</cell_line> in association with decreases in HIV-1 replication .


We conclude that soluble TNF receptors can inhibit stimuli-induced HIV-1 expression and NK- kappa B DNA-binding activity in chronically infected U1 cells .

We conclude that soluble TNF receptors can inhibit stimuli-induced HIV-1 expression and <protein>NK- kappa B</protein> DNA-binding activity in chronically <cell_type>infected U1 cells</cell_type> .


Transcriptional activation of RNA polymerase III-dependent genes by the human T-cell leukemia virus type 1 tax protein .

Transcriptional activation of <dna>RNA polymerase III-dependent genes</dna> by the <protein>human T-cell leukemia virus type 1 tax protein</protein> .


The human T-cell leukemia virus-encoded tax protein is a potent activator of many viral and cellular genes transcribed by RNA polymerase II .

The <protein>human T-cell leukemia virus-encoded tax protein</protein> is a potent activator of many <dna>viral and cellular genes</dna> transcribed by <protein>RNA polymerase II</protein> .


We find that both chromatin and cell extracts derived from human T-cell leukemia virus type 1-infected human T lymphocytes support higher levels of 5S rRNA and tRNA gene transcription than chromatin or extracts from uninfected T lymphocytes .

We find that both <dna>chromatin</dna> and cell extracts derived from <cell_line>human T-cell leukemia virus type 1-infected human T lymphocytes</cell_line> support higher levels of 5S rRNA and tRNA gene transcription than <dna>chromatin</dna> or extracts from <cell_type>uninfected T lymphocytes</cell_type> .


The viral protein Tax was likely responsible for this higher level of class II gene transcription , as purified Tax was found to stimulate both genes when added to the uninfected cell extract or in reconstituted systems .

The <protein>viral protein Tax</protein> was likely responsible for this higher level of <dna>class II gene</dna> transcription , as <protein>purified Tax</protein> was found to stimulate both genes when added to the uninfected cell extract or in reconstituted systems .


Both limiting-component transcription assays and DNA binding assays identified the class III gene transcription factor TFIIIB as the principle target of Tax activity .

Both limiting-component transcription assays and DNA binding assays identified the <protein>class III gene transcription factor</protein> <protein>TFIIIB</protein> as the principle target of <protein>Tax</protein> activity .


Surprisingly , we find that Tax increases the effective concentration of active TFIIIB molecules .

Surprisingly , we find that <protein>Tax</protein> increases the effective concentration of <protein>active TFIIIB molecules</protein> .


These data suggest that Tax stimulates RNA polymerase III-dependent gene expression by accelerating the rate and/or extent of transcription initiation complex assembly .

These data suggest that <protein>Tax</protein> stimulates <dna>RNA polymerase III-dependent gene</dna> expression by accelerating the rate and/or extent of <protein>transcription initiation complex</protein> assembly .


Expression of Retinoid X Receptor alpha is increased upon monocytic cell differentiation .

Expression of <protein>Retinoid X Receptor alpha</protein> is increased upon monocytic cell differentiation .


1 alpha , 25-Dihydroxyvitamin D3 ( VD ) is a potent inducer of monocytic differentiation of both normal and leukemic cells .

1 alpha , 25-Dihydroxyvitamin D3 ( VD ) is a potent inducer of monocytic differentiation of both <cell_type>normal and leukemic cells</cell_type> .


Its effects are mediated by its nuclear receptor ( VDR ) .

Its effects are mediated by its <protein>nuclear receptor</protein> ( <protein>VDR</protein> ) .


Efficient gene activation requires the heterodimerization of VDR with Retinoid X Receptors ( RXR ) .

Efficient gene activation requires the heterodimerization of <protein>VDR</protein> with <protein>Retinoid X Receptors</protein> ( <protein>RXR</protein> ) .


In the present study using specific antibodies , we analyzed the expression of the RXR alpha protein in blood mononuclear cells from acute myeloid patients ( AML ) ( 10 cases ) and from myelomonocytic cell lines arrested at different stages of differentiation .

In the present study using <protein>specific antibodies</protein> , we analyzed the expression of the <protein>RXR alpha protein</protein> in <cell_type>blood mononuclear cells</cell_type> from acute myeloid patients ( AML ) ( 10 cases ) and from <cell_line>myelomonocytic cell lines</cell_line> arrested at different stages of differentiation .


We observed that the RXR alpha expression increased during myelomonocytic differentiation , since the highest levels were found in AML samples and in myelomonocytic cell lines having the highest amounts of monocytic precursors .

We observed that the <protein>RXR alpha</protein> expression increased during myelomonocytic differentiation , since the highest levels were found in AML samples and in <cell_line>myelomonocytic cell lines</cell_line> having the highest amounts of <cell_type>monocytic precursors</cell_type> .


We also demonstrated that fresh leukemic cells , whatever their stage of differentiation , as well as myelomonocytic cell lines , respond to VD by an increase in RXR alpha levels .

We also demonstrated that fresh <cell_type>leukemic cells</cell_type> , whatever their stage of differentiation , as well as <cell_line>myelomonocytic cell lines</cell_line> , respond to VD by an increase in <protein>RXR alpha</protein> levels .


Combinations of all-trans retinoic acid ( RA ) and VD , in some cases , increased this effect .


This response suggests the involvement of RXR alpha in monocytic differentiation upon VD treatment .

This response suggests the involvement of <protein>RXR alpha</protein> in monocytic differentiation upon VD treatment .


Expression of p13MTCP1 is restricted to mature T-cell proliferations with t ( X ; 14 ) translocations .

Expression of <protein>p13MTCP1</protein> is restricted to mature T-cell proliferations with t ( X ; 14 ) translocations .