Five healthy human leukocyte antigen-B8 ( HLA-B8 ) -positive virus carriers were studied to investigate the CD8+ cytotoxic T lymphocyte ( CTL ) response to an HLA-B8-restricted peptide , RAKFKQLLQ , located in the Epstein-Barr virus ( EBV ) immediate-early trans-activator protein , BZLF1 .

Five healthy human leukocyte antigen-B8 ( HLA-B8 ) -positive virus carriers were studied to investigate the <cell_type>CD8+ cytotoxic T lymphocyte</cell_type> ( CTL ) response to an HLA-B8-restricted peptide , RAKFKQLLQ , located in the <protein>Epstein-Barr virus ( EBV ) immediate-early trans-activator protein</protein> , <protein>BZLF1</protein> .


Of the 5 virus carriers , 4 were infected with type A and 1 with type B EBV .


Using limiting-dilution analysis of peripheral blood mononuclear cells , a high RAKFKQLLQ-specific CTL precursor frequency was demonstrated after specific peptide or autologous lymphoblastoid cell line stimulation in both type A and type B EBV carriers .

Using limiting-dilution analysis of <cell_type>peripheral blood mononuclear cells</cell_type> , a high RAKFKQLLQ-specific CTL precursor frequency was demonstrated after specific peptide or autologous lymphoblastoid cell line stimulation in both type A and type B EBV carriers .


The RAKFKQLLQ-specific CTL precursor frequencies in all 5 persons were at least as dominant as those observed with two other EBV-associated , HLA-B8-restricted latent epitopes , FLRGRAYGL and QAKWRLQTL .

The RAKFKQLLQ-specific CTL precursor frequencies in all 5 persons were at least as dominant as those observed with two other <protein>EBV-associated , HLA-B8-restricted latent epitopes</protein> , FLRGRAYGL and QAKWRLQTL .


These findings show that healthy virus carriers maintain a high frequency of BZLF1-specific memory T cells , potentially to control virus spread from lytically infected cells .

These findings show that healthy virus carriers maintain a high frequency of <cell_type>BZLF1-specific memory T cells</cell_type> , potentially to control virus spread from <cell_type>lytically infected cells</cell_type> .


The DNA binding domain of the A-MYB transcription factor is responsible for its B cell-specific activity and binds to a B cell 110-kDa nuclear protein .

The <protein>DNA binding domain</protein> of the <protein>A-MYB</protein> <protein>transcription factor</protein> is responsible for its B cell-specific activity and binds to a <protein>B cell 110-kDa nuclear protein</protein> .


Expression studies as well as the use of transgenic animals have demonstrated that the A-MYB transcription factor plays central and specific role in the regulation of mature B cell proliferation and/or differentiation .

Expression studies as well as the use of transgenic animals have demonstrated that the <protein>A-MYB</protein> <protein>transcription factor</protein> plays central and specific role in the regulation of <cell_type>mature B cell</cell_type> proliferation and/or differentiation .


Furthermore , it is highly expressed in Burkitt 's lymphoma cells and may participate in the pathogenesis of this disease .

Furthermore , it is highly expressed in <cell_line>Burkitt 's lymphoma cells</cell_line> and may participate in the pathogenesis of this disease .


We have therefore investigated the transcriptional activity of A-MYB and its regulation in several human lymphoid cell lines using co-transfection assays and show that A-MYB is transcriptionally active in all the B cell lines studied , but not in T cells .

We have therefore investigated the transcriptional activity of <protein>A-MYB</protein> and its regulation in several <cell_line>human lymphoid cell lines</cell_line> using co-transfection assays and show that <protein>A-MYB</protein> is transcriptionally active in all the <cell_line>B cell lines</cell_line> studied , but not in <cell_type>T cells</cell_type> .


In particular the best responder cell line was the Burkitt 's cell line Namalwa .

In particular the best <cell_line>responder cell line</cell_line> was the <cell_line>Burkitt 's cell line Namalwa</cell_line> .


The activity of A-MYB in B and not T cells was observed when either an artificial construct or the c-MYC promoter was used as a reporter .

The activity of <protein>A-MYB</protein> in <cell_type>B and not T cells</cell_type> was observed when either an artificial construct or the <dna>c-MYC promoter</dna> was used as a reporter .


Furthermore , the functional domains responsible for DNA binding , transactivation , and negative regulation , previously characterized in a fibroblast context , were found to have similar activity in B cells .

Furthermore , the <protein>functional domains</protein> responsible for DNA binding , transactivation , and negative regulation , previously characterized in a fibroblast context , were found to have similar activity in <cell_type>B cells</cell_type> .


The region of A-MYB responsible for the B cell specific activity was defined to be the N-terminal 218 amino acids containing the DNA binding domain .

The region of <protein>A-MYB</protein> responsible for the B cell specific activity was defined to be the <protein>N-terminal 218 amino acids</protein> containing the <protein>DNA binding domain</protein> .


Finally , a 110-kDa protein has been identified in the nuclei of all the B , but not T , cell lines that specifically binds to this A-MYB N-terminal domain .

Finally , a <protein>110-kDa protein</protein> has been identified in the nuclei of all the <cell_line>B , but not T , cell lines</cell_line> that specifically binds to this <protein>A-MYB N-terminal domain</protein> .


We hypothesize that this 110-kDa protein may be a functionally important B cell-specific co-activator of A-MYB .

We hypothesize that this <protein>110-kDa protein</protein> may be a functionally important <protein>B cell-specific co-activator</protein> of <protein>A-MYB</protein> .


Transcription factor Egr-1 activity down-regulates Fas and CD23 expression in B cells .

Transcription factor <protein>Egr-1</protein> activity down-regulates Fas and CD23 expression in <cell_type>B cells</cell_type> .


Activation of mature B cells via Ag receptor cross-linking induces transient expression of the transcription factor Egr-1 .

Activation of mature <cell_type>B cells</cell_type> via <protein>Ag receptor</protein> cross-linking induces transient expression of the <protein>transcription factor</protein> <protein>Egr-1</protein> .


Although the activating signals leading to Egr-1 induction have been studied extensively , little is known about the genes that are placed further downstream within this activation cascade and that are transcriptionally regulated by Egr-1 .

Although the activating signals leading to <protein>Egr-1</protein> induction have been studied extensively , little is known about the genes that are placed further downstream within this activation cascade and that are transcriptionally regulated by <protein>Egr-1</protein> .


To identify such target genes , we established Egr-1-overexpressing transfectants from the murine B cell line K46 and from human Ramos B cells .

To identify such <dna>target genes</dna> , we established <cell_line>Egr-1-overexpressing transfectants</cell_line> from the <cell_line>murine B cell line K46</cell_line> and from <cell_line>human Ramos B cells</cell_line> .


All clones derived from K46 B cells showed increased expression of CD44 .

All clones derived from <cell_line>K46 B cells</cell_line> showed increased expression of <protein>CD44</protein> .


Most interestingly , expression of CD95 ( Fas/Apo-1 ) and of CD23 was down-regulated in all K46 transfectants .

Most interestingly , expression of <protein>CD95</protein> ( <protein>Fas/Apo-1</protein> ) and of <protein>CD23</protein> was down-regulated in all <cell_line>K46 transfectants</cell_line> .


As a consequence , they became resistant to apoptosis induced by anti-CD95 Ab treatment .

As a consequence , they became resistant to apoptosis induced by <protein>anti-CD95 Ab</protein> treatment .


Similarly , the Egr-1-expressing Ramos cells showed reduced levels of CD95 expression .

Similarly , the <cell_line>Egr-1-expressing Ramos cells</cell_line> showed reduced levels of <protein>CD95</protein> expression .


Thus , Egr-1 seems to control the expression of downstream target genes not only as a transcriptional activator , but also as a repressor molecule .

Thus , <protein>Egr-1</protein> seems to control the expression of <dna>downstream target genes</dna> not only as a transcriptional activator , but also as a <protein>repressor molecule</protein> .


In B cells , Egr-1 therefore plays a critical role in integrating the short-lived signal delivered by triggering of the Ag receptor into phenotypic changes , including repression of CD95 and CD23 transcription .

In <cell_type>B cells</cell_type> , <protein>Egr-1</protein> therefore plays a critical role in integrating the short-lived signal delivered by triggering of the <protein>Ag receptor</protein> into phenotypic changes , including repression of <protein>CD95</protein> and <protein>CD23</protein> transcription .


Regulation of NF-kappa B activity by I kappa B alpha and I kappa B beta stability .

Regulation of <protein>NF-kappa B</protein> activity by I kappa B alpha and I kappa B beta stability .


Transcription factor NF-kappa B must be released from cytoplasmic inhibitory molecules ( I kappa Bs ) in order to move to the nucleus and to activate its target genes .

<protein>Transcription factor</protein> <protein>NF-kappa B</protein> must be released from <protein>cytoplasmic inhibitory molecules</protein> ( <protein>I kappa Bs</protein> ) in order to move to the nucleus and to activate its <dna>target genes</dna> .


Little is known about the mechanisms regulating the maintenance of constitutive nuclear NF-kappa B in some cell-types and of sustained nuclear NF-kappa B activity after stimulation .

Little is known about the mechanisms regulating the maintenance of <protein>constitutive nuclear NF-kappa B</protein> in some cell-types and of sustained nuclear <protein>NF-kappa B</protein> activity after stimulation .


Increased turnover has been implicated in the regulation of constitutive NF-kappa B activity in mature B cells .

Increased turnover has been implicated in the regulation of constitutive <protein>NF-kappa B</protein> activity in <cell_type>mature B cells</cell_type> .


We therefore compared the turnover of I kappa B alpha and I kappa B beta in mature B cells and HeLa cells .

We therefore compared the turnover of <protein>I kappa B alpha</protein> and <protein>I kappa B beta</protein> in <cell_type>mature B cells</cell_type> and <cell_line>HeLa cells</cell_line> .


Both proteins display a high turnover in B cells although I kappa B beta is considerably more stable than I kappa B alpha .

Both proteins display a high turnover in <cell_type>B cells</cell_type> although <protein>I kappa B beta</protein> is considerably more stable than <protein>I kappa B alpha</protein> .


The half-life of both inhibitors is increased in HeLa cells .

The half-life of both inhibitors is increased in <cell_line>HeLa cells</cell_line> .


In contrast , all other NF-kappa B /I kappa B molecules tested are relatively stable in both cell-types .

In contrast , all other <protein>NF-kappa B</protein> /I kappa B molecules tested are relatively stable in both cell-types .


The elevated turnover of endogenous I kappa B alpha in Namalwa cells is inhibited by a proteasome inhibitor and thus seems to be driven by the same degradation machinery as the slower turnover in non-B cells .

The elevated turnover of endogenous <protein>I kappa B alpha</protein> in <cell_type>Namalwa cells</cell_type> is inhibited by a proteasome inhibitor and thus seems to be driven by the same degradation machinery as the slower turnover in <cell_type>non-B cells</cell_type> .


Furthermore , we investigated the processes involved in persistent activation of NF-kappa B .

Furthermore , we investigated the processes involved in persistent activation of <protein>NF-kappa B</protein> .


TNF-alpha signaling leads to a rapid depletion of cellular I kappa B beta pools .

TNF-alpha signaling leads to a rapid depletion of cellular <protein>I kappa B beta</protein> pools .


I kappa B alpha is efficiently resynthesized whereas I kappa B beta levels stay low for a prolonged time .

<protein>I kappa B alpha</protein> is efficiently resynthesized whereas <protein>I kappa B beta</protein> levels stay low for a prolonged time .


NF-kappa B binding activity can be detected for several hours after stimulation .

<protein>NF-kappa B</protein> binding activity can be detected for several hours after stimulation .


We found that removal of the TNF-alpha containing medium causes a rapid decrease in nuclear NF-kappa B .

We found that removal of the <protein>TNF-alpha</protein> containing medium causes a rapid decrease in <protein>nuclear NF-kappa B</protein> .


A phosphoform of newly synthesized I kappa B alpha is visible when degradation by the proteasome is inhibited and new I kappa B alpha displays the same properties regarding phosphorylation and degradation in response to a second inducer .

A phosphoform of newly synthesized <protein>I kappa B alpha</protein> is visible when degradation by the <protein>proteasome</protein> is inhibited and new <protein>I kappa B alpha</protein> displays the same properties regarding phosphorylation and degradation in response to a second inducer .


There is no significant difference in the turnover of pre- and post-inductive I kappa B alpha .

There is no significant difference in the turnover of pre- and post-inductive <protein>I kappa B alpha</protein> .


These observations suggest that resynthesis of I kappa B alpha and removal of the stimulus are obligatory steps for the inactivation of nuclear NF kappa B .

These observations suggest that resynthesis of <protein>I kappa B alpha</protein> and removal of the stimulus are obligatory steps for the inactivation of <protein>nuclear NF kappa B</protein> .


Selection of a diverse TCR repertoire in response to an Epstein-Barr virus-encoded transactivator protein BZLF1 by CD8+ cytotoxic T lymphocytes during primary and persistent infection .

Selection of a diverse <protein>TCR repertoire</protein> in response to an <protein>Epstein-Barr virus-encoded transactivator protein</protein> <protein>BZLF1</protein> by <cell_type>CD8+ cytotoxic T lymphocytes</cell_type> during primary and persistent infection .


We investigated the CD8+ cytotoxic T lymphocyte ( CTL ) repertoire to an HLA B8-restricted peptide , RAKFKQLLQ , located in the Epstein-Barr virus ( EBV ) immediate-early protein , BZLF1 .

We investigated the <protein>CD8+ cytotoxic T lymphocyte ( CTL ) repertoire</protein> to an HLA B8-restricted peptide , RAKFKQLLQ , located in the <protein>Epstein-Barr virus ( EBV ) immediate-early protein</protein> , <protein>BZLF1</protein> .


Repertoire selection was monitored by determining the TCR beta chain sequences of RAKFKQLLQ-specific CTL established from primary infected and healthy virus carriers .

Repertoire selection was monitored by determining the <protein>TCR beta chain sequences</protein> of <cell_line>RAKFKQLLQ-specific CTL</cell_line> established from primary infected and healthy virus carriers .


PCR analysis of spontaneous EBV-transformed lymphoblastoid cell lines ( LCL ) from three individuals with primary infection showed that two were infected with type A and one with type B EBV .

PCR analysis of <cell_line>spontaneous EBV-transformed lymphoblastoid cell lines</cell_line> ( <cell_line>LCL</cell_line> ) from three individuals with primary infection showed that two were infected with type A and one with type B EBV .


Polyclonal and clonal CTL that were generated by stimulating peripheral blood mononuclear cells with an HLA B8+ homozygous LCL lysed T cell blasts pulsed with the peptide , RAKFKQLLQ ; lysis of certain HLA B8+ LCL targets was associated with the abundance of BZLF1 transcripts .

<cell_line>Polyclonal and clonal CTL</cell_line> that were generated by stimulating <cell_type>peripheral blood mononuclear cells</cell_type> with an <cell_line>HLA B8+ homozygous LCL lysed T cell blasts</cell_line> pulsed with the peptide , RAKFKQLLQ ; lysis of certain HLA B8+ LCL targets was associated with the abundance of <rna>BZLF1 transcripts</rna> .


TCR beta analysis showed that while there was loop length restriction in the putative peptide contact site of all responding beta chains , diverse and unique ( non-recurrent ) TCR beta clonotypes were selected in individuals during primary infection and continued to emerge after long-term virus exposure .

<dna>TCR beta</dna> analysis showed that while there was loop length restriction in the putative peptide contact site of all responding <protein>beta chains</protein> , diverse and <cell_line>unique ( non-recurrent ) TCR beta clonotypes</cell_line> were selected in individuals during primary infection and continued to emerge after long-term virus exposure .


TCR -contact site heterogeneity was excluded as the selective force in diversity generation since the epitope-encoded sequences were found to be identical within endogenous virus isolates .

<protein>TCR</protein> -contact site heterogeneity was excluded as the selective force in diversity generation since the epitope-encoded sequences were found to be identical within endogenous virus isolates .


In this first study of TCR repertoire selection for an EBV lytic antigen , a BZLF1 -reactive component of diverse clonotypes was identified in primary type A or type B EBV infection which was sustained in the EBV-specific memory response throughout life-long infection .

In this first study of <protein>TCR repertoire</protein> selection for an <protein>EBV lytic antigen</protein> , a <protein>BZLF1</protein> -reactive component of diverse clonotypes was identified in primary type A or type B EBV infection which was sustained in the EBV-specific memory response throughout life-long infection .


This diversity selection is likely to play a critical role in maintaining a balanced viral load throughout EBV persistence .


Molecular mechanisms of anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells .

Molecular mechanisms of anoxia/reoxygenation-induced neutrophil adherence to <cell_line>cultured endothelial cells</cell_line> .


The objectives of this study were to ( 1 ) determine the time course of neutrophil adhesion to monolayers of human umbilical vein endothelial cells ( HUVECs ) that were exposed to 60 minutes of anoxia followed by 30 to 600 minutes of reoxygenation and ( 2 ) define the mechanisms responsible for both the early ( minutes ) and late ( hours ) hyperadhesivity of postanoxic HUVECs to human neutrophils .

The objectives of this study were to ( 1 ) determine the time course of neutrophil adhesion to monolayers of <cell_line>human umbilical vein endothelial cells</cell_line> ( <cell_line>HUVECs</cell_line> ) that were exposed to 60 minutes of anoxia followed by 30 to 600 minutes of reoxygenation and ( 2 ) define the mechanisms responsible for both the early ( minutes ) and late ( hours ) hyperadhesivity of <cell_line>postanoxic HUVECs</cell_line> to <cell_type>human neutrophils</cell_type> .


The results clearly demonstrate that anoxia/reoxygenation ( A/R ) leads to a biphasic increase in neutrophil adhesion to HUVECs , with peak responses occurring at 30 minutes ( phase 1 ) and 240 minutes ( phase 2 ) after reoxygenation .

The results clearly demonstrate that anoxia/reoxygenation ( A/R ) leads to a biphasic increase in neutrophil adhesion to <cell_line>HUVECs</cell_line> , with peak responses occurring at 30 minutes ( phase 1 ) and 240 minutes ( phase 2 ) after reoxygenation .


Oxypurinol and catalase inhibited phase-1 adhesion , suggesting a role for xanthine oxidase and H2O2 .

Oxypurinol and <protein>catalase</protein> inhibited phase-1 adhesion , suggesting a role for <protein>xanthine oxidase</protein> and H2O2 .


In comparison , platelet activating factor ( PAF ) contributed to both phases of neutrophil adhesion .

In comparison , <protein>platelet activating factor</protein> ( <protein>PAF</protein> ) contributed to both phases of neutrophil adhesion .


Anti-intercellular adhesion molecule-1 ( ICAM-1 ) and anti-P-selectin antibodies ( monoclonal antibodies [ mAbs ] ) attenuated phase-1 neutrophil adhesion , consistent with roles for constitutively expressed ICAM-1 and enhanced surface expression of preformed P-selectin .

<protein>Anti-intercellular adhesion molecule-1</protein> ( <protein>ICAM-1</protein> ) and <protein>anti-P-selectin antibodies</protein> ( <protein>monoclonal antibodies</protein> [ <protein>mAbs</protein> ] ) attenuated phase-1 neutrophil adhesion , consistent with roles for constitutively expressed <protein>ICAM-1</protein> and enhanced surface expression of preformed <protein>P-selectin</protein> .


Phase-2 neutrophil adhesion was attenuated by an anti-E-selectin mAb , indicating a dominant role of this adhesion molecule in the late phase response .

Phase-2 neutrophil adhesion was attenuated by an <protein>anti-E-selectin mAb</protein> , indicating a dominant role of this adhesion molecule in the late phase response .


Pretreatment with actinomycin D and cycloheximide or with competing ds-oligonucleotides containing the nuclear factor-kappa B or activator protein-1 cognate DNA sequences significantly attenuated phase-2 response , suggesting a role for de novo macromolecule synthesis .

Pretreatment with actinomycin D and cycloheximide or with competing ds-oligonucleotides containing the <protein>nuclear factor-kappa B</protein> or <protein>activator protein-1</protein> <dna>cognate DNA sequences</dna> significantly attenuated phase-2 response , suggesting a role for de novo macromolecule synthesis .


Surface expression of ICAM-1 , P-selectin , and E-selectin on HUVECs correlated with the phase-1 and -2 neutrophil adhesion responses .

Surface expression of <protein>ICAM-1</protein> , <protein>P-selectin</protein> , and <protein>E-selectin</protein> on <cell_line>HUVECs</cell_line> correlated with the phase-1 and -2 neutrophil adhesion responses .


Collectively , these findings indicate that A/R elicits a two-phase neutrophil-endothelial cell adhesion response that involves transcription-independent and transcription-dependent surface expression of different endothelial cell adhesion molecules .

Collectively , these findings indicate that A/R elicits a two-phase neutrophil-endothelial cell adhesion response that involves transcription-independent and transcription-dependent surface expression of different <protein>endothelial cell adhesion molecules</protein> .


Characterization of CD40 signaling determinants regulating nuclear factor-kappa B activation in B lymphocytes .

Characterization of <protein>CD40</protein> signaling determinants regulating <protein>nuclear factor-kappa B</protein> activation in <cell_type>B lymphocytes</cell_type> .


CD40 signaling to B cells is important for generating an effective humoral immune response .

<protein>CD40</protein> signaling to <cell_type>B cells</cell_type> is important for generating an effective humoral immune response .


CD40 ligation leads to B cell activation events such as proliferation , Ig secretion , isotype switching , and up-regulation of cell surface molecules , as well as the generation of memory B cells .

<protein>CD40</protein> ligation leads to B cell activation events such as proliferation , Ig secretion , isotype switching , and up-regulation of <protein>cell surface molecules</protein> , as well as the generation of <cell_type>memory B cells</cell_type> .


Many of these events are dependent upon the ability of CD40 to activate the transcription factor NF-kappa B ( NF-kappa B ) .

Many of these events are dependent upon the ability of <protein>CD40</protein> to activate the transcription factor <protein>NF-kappa B</protein> ( <protein>NF-kappa B</protein> ) .


To define the CD40 signaling components upstream of NF-kappa B activation and the functional consequences downstream of NF-kappa B activation , we examined mouse B cell transfectants expressing wild-type or mutant human CD40 .

To define the <protein>CD40</protein> signaling components upstream of <protein>NF-kappa B</protein> activation and the functional consequences downstream of <protein>NF-kappa B</protein> activation , we examined <cell_line>mouse B cell transfectants</cell_line> expressing <protein>wild-type or mutant human CD40</protein> .


Analysis of CD40 cytoplasmic domain truncation and point mutants defined a 10-amino acid CD40 cytoplasmic signaling determinant required for NF-kappa B activation .

Analysis of <protein>CD40 cytoplasmic domain</protein> truncation and point mutants defined a <protein>10-amino acid CD40 cytoplasmic signaling determinant</protein> required for <protein>NF-kappa B</protein> activation .


A threonine residue at position 234 , previously shown to be important for CD40 association with TNF receptor-associated factor 2 ( TRAF2 ) , TRAF3 , and TRAF5 , was not required for NF-kappa B activation .

A threonine residue at <protein>position 234</protein> , previously shown to be important for <protein>CD40</protein> association with <protein>TNF receptor-associated factor 2</protein> ( <protein>TRAF2</protein> ) , <protein>TRAF3</protein> , and <protein>TRAF5</protein> , was not required for <protein>NF-kappa B</protein> activation .


This suggests that in B cells , CD40 -induced NF-kappa B activation can occur independently of TRAF2 and TRAF5 association .

This suggests that in <cell_type>B cells</cell_type> , <protein>CD40</protein> -induced <protein>NF-kappa B</protein> activation can occur independently of <protein>TRAF2</protein> and <protein>TRAF5</protein> association .


NF-kappa B activation was independent of the transmembrane domain of CD40 , suggesting that it is independent of p23 , a molecule that associates with CD40 in a region other than the cytoplasmic domain .

<protein>NF-kappa B</protein> activation was independent of the <protein>transmembrane domain</protein> of <protein>CD40</protein> , suggesting that it is independent of <protein>p23</protein> , a molecule that associates with <protein>CD40</protein> in a region other than the <protein>cytoplasmic domain</protein> .


Proteasome-dependent inhibitory kappa B alpha ( I kappa B alpha ) and I kappa B beta degradation occurred downstream of CD40 ligation and preceded CD40 -mediated NF-kappa B nuclear translocation .

Proteasome-dependent inhibitory kappa B alpha ( <protein>I kappa B alpha</protein> ) and <protein>I kappa B beta</protein> degradation occurred downstream of <protein>CD40</protein> ligation and preceded <protein>CD40</protein> -mediated <protein>NF-kappa B</protein> nuclear translocation .


CD40- or pervanadate-mediated I kappa B tyrosine phosphorylation was not detected .


NF-kappa B activation correlated with the ability of CD40 to induce Ab secretion and the up-regulation of ICAM-1 and LFA-1 .

<protein>NF-kappa B</protein> activation correlated with the ability of <protein>CD40</protein> to induce Ab secretion and the up-regulation of <protein>ICAM-1</protein> and <protein>LFA-1</protein> .


However , NF-kappa B activation was insufficient for CD40 -mediated up-regulation of B7-1 , Fas , and CD23 .

However , <protein>NF-kappa B</protein> activation was insufficient for <protein>CD40</protein> -mediated up-regulation of <protein>B7-1</protein> , <protein>Fas</protein> , and <protein>CD23</protein> .


CD30 -dependent degradation of TRAF2 : implications for negative regulation of TRAF signaling and the control of cell survival .

<protein>CD30</protein> -dependent degradation of <protein>TRAF2</protein> : implications for negative regulation of <protein>TRAF</protein> signaling and the control of cell survival .


CD30 is a cell-surface receptor that can augment lymphocyte activation and survival through its ability to induce the transcription factor NF-kappaB .

<protein>CD30</protein> is a <protein>cell-surface receptor</protein> that can augment lymphocyte activation and survival through its ability to induce the <protein>transcription factor</protein> <protein>NF-kappaB</protein> .


CD30 , however , has also been implicated in the induction of apoptotic cell death of lymphocytes .

<protein>CD30</protein> , however , has also been implicated in the induction of apoptotic cell death of <cell_type>lymphocytes</cell_type> .


Here we show that one of the effects of CD30 signal transduction is to render cells sensitive to apoptosis induced by the type 1 tumor necrosis factor receptor ( TNFR1 ) .

Here we show that one of the effects of <protein>CD30</protein> signal transduction is to render cells sensitive to apoptosis induced by the <protein>type 1 tumor necrosis factor receptor</protein> ( <protein>TNFR1</protein> ) .


This sensitization is dependent on the TRAF-binding sites within the CD30 cytoplasmic domain .

This sensitization is dependent on the <protein>TRAF-binding sites</protein> within the <protein>CD30</protein> <protein>cytoplasmic domain</protein> .


One of the proteins that binds to these sites is TRAF2 , a signal transduction molecule that is also utilized by TNFR1 to mediate the activation of several downstream kinases and transcription factors .

One of the proteins that binds to these sites is <protein>TRAF2</protein> , a <protein>signal transduction molecule</protein> that is also utilized by <protein>TNFR1</protein> to mediate the activation of several downstream <protein>kinases</protein> and <protein>transcription factors</protein> .


During CD30 signal transduction , we found that binding of TRAF2 to the cytoplasmic domain of CD30 results in the rapid depletion of TRAF2 and the associated protein TRAF1 by proteolysis .

During <protein>CD30</protein> signal transduction , we found that binding of <protein>TRAF2</protein> to the <protein>cytoplasmic domain</protein> of <protein>CD30</protein> results in the rapid depletion of <protein>TRAF2</protein> and the associated protein <protein>TRAF1</protein> by proteolysis .


These data suggest a model in which CD30 limits its own ability to transduce cell survival signals through signal-coupled depletion of TRAF2 .

These data suggest a model in which <protein>CD30</protein> limits its own ability to transduce cell survival signals through signal-coupled depletion of <protein>TRAF2</protein> .


Depletion of intracellular TRAF2 and its coassociated proteins also increased the sensitivity of the cell to undergoing apoptosis during activation of death-inducing receptors such as TNFR1 .

Depletion of intracellular <protein>TRAF2</protein> and its <protein>coassociated proteins</protein> also increased the sensitivity of the cell to undergoing apoptosis during activation of <protein>death-inducing receptors</protein> such as <protein>TNFR1</protein> .


Consistent with this hypothesis , expression of a dominant-negative form of TRAF2 was found to potentiate TNFR1 -mediated death .

Consistent with this hypothesis , expression of a <protein>dominant-negative form</protein> of <protein>TRAF2</protein> was found to potentiate <protein>TNFR1</protein> -mediated death .


These studies provide a potential mechanism through which CD30 , as well as other TRAF-binding members of the TNFR superfamily , can negatively regulate cell survival .

These studies provide a potential mechanism through which <protein>CD30</protein> , as well as other <protein>TRAF-binding members</protein> of the <protein>TNFR superfamily</protein> , can negatively regulate cell survival .


Analysis of myeloid-associated genes in human hematopoietic progenitor cells .

Analysis of <dna>myeloid-associated genes</dna> in <cell_type>human hematopoietic progenitor cells</cell_type> .


The distribution of myeloid lineage-associated cytokine receptors and lysosomal proteins was analyzed in human CD34+ cord blood cell ( CB ) subsets at different stages of myeloid commitment by reverse-transcriptase polymerase chain reaction ( RT-PCR ) .

The distribution of <protein>myeloid lineage-associated cytokine receptors</protein> and <protein>lysosomal proteins</protein> was analyzed in <cell_line>human CD34+ cord blood cell ( CB ) subsets</cell_line> at different stages of myeloid commitment by reverse-transcriptase polymerase chain reaction ( RT-PCR ) .


The highly specific granulomonocyte-associated lysosomal proteins myeloperoxidase ( MPO ) and lysozyme ( LZ ) , as well as the transcription factor PU.1 , were already detectable in the most immature CD34+Thy-1+ subset .

The highly specific <protein>granulomonocyte-associated lysosomal proteins</protein> <protein>myeloperoxidase</protein> ( <protein>MPO</protein> ) and <protein>lysozyme</protein> ( <protein>LZ</protein> ) , as well as the <protein>transcription factor</protein> <protein>PU.1</protein> , were already detectable in the most immature <cell_line>CD34+Thy-1+ subset</cell_line> .


Messenger RNA ( mRNA ) levels for the granulocyte-colony stimulating factor ( G-CSF ) receptor , granulocyte-macrophage ( GM ) -CSF receptor alpha subunit and tumor necrosis factor ( TNF ) receptors I ( p55 ) and II ( p75 ) were also detected in this subset in addition to c-kit and flt-3 , receptors known to be expressed on progenitor cells .

<rna>Messenger RNA</rna> ( <rna>mRNA</rna> ) levels for the <protein>granulocyte-colony stimulating factor ( G-CSF ) receptor</protein> , <protein>granulocyte-macrophage ( GM ) -CSF receptor alpha subunit</protein> and <protein>tumor necrosis factor ( TNF ) receptors I ( p55 ) and II ( p75 )</protein> were also detected in this subset in addition to <protein>c-kit</protein> and <protein>flt-3</protein> , receptors known to be expressed on <cell_type>progenitor cells</cell_type> .


By contrast , the monocyte-macrophage colony stimulating factor ( M-CSF ) receptor was largely absent at this stage and in the CD34+Thy-1-CD45RA- subsets .

By contrast , the <protein>monocyte-macrophage colony stimulating factor ( M-CSF ) receptor</protein> was largely absent at this stage and in the <cell_line>CD34+Thy-1-CD45RA- subsets</cell_line> .


The M-CSF receptor was first detectable in the myeloid-committed CD34+Thy-l-CD45RA+ subset .

The <protein>M-CSF receptor</protein> was first detectable in the <cell_line>myeloid-committed CD34+Thy-l-CD45RA+ subset</cell_line> .


All other molecules studied were found to be expressed at this stage of differentiation .


Different cocktails of the identified ligands were added to sorted CD34+Thy-1+ single cells .

Different cocktails of the identified ligands were added to <cell_line>sorted CD34+Thy-1+ single cells</cell_line> .


Low proliferative capacity was observed after 1 week in culture in the presence of stem cell factor ( SCF ) + Flt-3 ligand ( FL ) + G-CSF .

Low proliferative capacity was observed after 1 week in culture in the presence of <protein>stem cell factor</protein> ( <protein>SCF</protein> ) + <protein>Flt-3 ligand</protein> ( <protein>FL</protein> ) + <protein>G-CSF</protein> .


Addition of GM-CSF to this basic cocktail consistently increased the clonogenic capacity of single CD34+Thy-1+ cells , and this effect was further enhanced ( up to 72.3 +/- 4.3 % on day 7 ) by the inclusion of TNF-alpha .

Addition of <protein>GM-CSF</protein> to this basic cocktail consistently increased the clonogenic capacity of <cell_line>single CD34+Thy-1+ cells</cell_line> , and this effect was further enhanced ( up to 72.3 +/- 4.3 % on day 7 ) by the inclusion of <protein>TNF-alpha</protein> .


In conclusion , the presence of myeloid-associated growth factor receptor transcripts in CD34+ CB subsets does not discriminate the various stages of differentiation , with the exception of the M-CSF receptor .

In conclusion , the presence of <rna>myeloid-associated growth factor receptor transcripts</rna> in <cell_line>CD34+ CB subsets</cell_line> does not discriminate the various stages of differentiation , with the exception of the <protein>M-CSF receptor</protein> .


In addition , we show that TNF-alpha is a potent costimulatory factor of the very immature CD34+Thy-1+ CB subset .

In addition , we show that <protein>TNF-alpha</protein> is a potent costimulatory factor of the very <cell_line>immature CD34+Thy-1+ CB subset</cell_line> .


Induction of endothelial cell surface adhesion molecules by tumor necrosis factor is blocked by protein tyrosine phosphatase inhibitors : role of the nuclear transcription factor NF-kappa B .

Induction of <protein>endothelial cell surface adhesion molecules</protein> by <protein>tumor necrosis factor</protein> is blocked by protein tyrosine phosphatase inhibitors : role of the <protein>nuclear transcription factor NF-kappa B</protein> .


Recent studies from our laboratory have indicated that protein tyrosine phosphatase ( PTPase ) inhibitors can down-modulate the tumor necrosis factor ( TNF ) -mediated activation of the nuclear transcription factor NF-kappa B in ML-1a , a monocytic cell line ( Singh and Aggarwal , J. Biol. Chem. 1995 : 270 : 10631 ) .

Recent studies from our laboratory have indicated that <protein>protein tyrosine phosphatase</protein> ( <protein>PTPase</protein> ) inhibitors can down-modulate the <protein>tumor necrosis factor</protein> ( <protein>TNF</protein> ) -mediated activation of the <protein>nuclear transcription factor NF-kappa B</protein> in <cell_line>ML-1a</cell_line> , a <cell_line>monocytic cell line</cell_line> ( Singh and Aggarwal , J. Biol. Chem. 1995 : 270 : 10631 ) .


Since TNF is one of the major inducers of various adhesion molecules in human endothelial cells and their expression is known to require the activation of NF-kappa B , we examined the effect of PTPase inhibitors on the TNF -mediated induction of intracellular adhesion molecule ( ICAM ) -1 , vascular cell adhesion molecule ( VCAM ) -1 and endothelial leukocyte adhesion molecule ( ELAM ) -1 .

Since <protein>TNF</protein> is one of the major inducers of various <protein>adhesion molecules</protein> in human endothelial cells and their expression is known to require the activation of <protein>NF-kappa B</protein> , we examined the effect of <protein>PTPase</protein> inhibitors on the <protein>TNF</protein> -mediated induction of <protein>intracellular adhesion molecule ( ICAM ) -1</protein> , <protein>vascular cell adhesion molecule ( VCAM ) -1</protein> and <protein>endothelial leukocyte adhesion molecule ( ELAM ) -1</protein> .


Like ML-1a , human dermal microvessel endothelial cells ( MVEC ) treated with TNF rapidly activated ( within 30 min ) NF-kappa B ; this effect was completely abolished by co-treatment with phenylarsine oxide ( PAO ) , a specific inhibitor of PTPase .

Like <cell_line>ML-1a</cell_line> , <cell_line>human dermal microvessel endothelial cells</cell_line> ( <cell_line>MVEC</cell_line> ) treated with <protein>TNF</protein> rapidly activated ( within 30 min ) <protein>NF-kappa B</protein> ; this effect was completely abolished by co-treatment with phenylarsine oxide ( PAO ) , a specific inhibitor of <protein>PTPase</protein> .


The induction of ICAM-1 , VCAM-1 , and ELAM-1 by TNF in MVEC occurred within 6 h and was also completely down-regulated by PAO in a dose-dependent manner .

The induction of <protein>ICAM-1</protein> , <protein>VCAM-1</protein> , and <protein>ELAM-1</protein> by <protein>TNF</protein> in <cell_line>MVEC</cell_line> occurred within 6 h and was also completely down-regulated by PAO in a dose-dependent manner .


PAO was found to be effective even when added 3 h after TNF , suggesting a rapid mode of action of this inhibitor .

PAO was found to be effective even when added 3 h after <protein>TNF</protein> , suggesting a rapid mode of action of this inhibitor .


Besides PAO , other inhibitors of PTPase , including pervanadate and diamide , also blocked TNF -dependent NF-kappa B activation and induction of all the three adhesion proteins .

Besides PAO , other inhibitors of <protein>PTPase</protein> , including pervanadate and diamide , also blocked <protein>TNF</protein> -dependent <protein>NF-kappa B</protein> activation and induction of all the three <protein>adhesion proteins</protein> .


Consistent with these results , the attachment of monocytes to MVEC was also blocked by the PTPase inhibitors .

Consistent with these results , the attachment of monocytes to <cell_line>MVEC</cell_line> was also blocked by the <protein>PTPase</protein> inhibitors .


Thus , overall , our results demonstrate that a PTPase is involved either directly or indirectly in the pathway leading to the induction of endothelial cell adhesion molecules by TNF .

Thus , overall , our results demonstrate that a <protein>PTPase</protein> is involved either directly or indirectly in the pathway leading to the induction of <protein>endothelial cell adhesion molecules</protein> by <protein>TNF</protein> .


Because of their role in cell adhesion , PTPase may provide a novel target of drug development for treatment of inflammation , atherogenesis , and tumor metastasis .

Because of their role in cell adhesion , <protein>PTPase</protein> may provide a novel target of drug development for treatment of inflammation , atherogenesis , and tumor metastasis .


Regulation of nuclear factor-kappa B and its inhibitor I kappa B-alpha/MAD-3 in monocytes by Mycobacterium tuberculosis and during human tuberculosis .

Regulation of <protein>nuclear factor-kappa B</protein> and its inhibitor <protein>I kappa B-alpha/MAD-3</protein> in <cell_type>monocytes</cell_type> by Mycobacterium tuberculosis and during human tuberculosis .


Blood monocytes from patients with active tuberculosis are activated in vivo , as evidenced by an increase in the stimulated release of proinflammatory cytokines , such as TNF-alpha , and the spontaneous expression of IL-2R .

<cell_type>Blood monocytes</cell_type> from patients with active tuberculosis are activated in vivo , as evidenced by an increase in the stimulated release of <protein>proinflammatory cytokines</protein> , such as <protein>TNF-alpha</protein> , and the spontaneous expression of <protein>IL-2R</protein> .


Further , monocytes from patients demonstrate an augmented susceptibility to a productive infection with HIV-1 in vitro .

Further , <cell_type>monocytes</cell_type> from patients demonstrate an augmented susceptibility to a productive infection with HIV-1 in vitro .


Mycobacterium tuberculosis and its components are strong signals to activate monocytes to production of cytokines .

Mycobacterium tuberculosis and its components are strong signals to activate <cell_type>monocytes</cell_type> to production of <protein>cytokines</protein> .


In this study we examined the basis of activation of monocytes during active tuberculosis and by M. tuberculosis .

In this study we examined the basis of activation of <cell_type>monocytes</cell_type> during active tuberculosis and by M. tuberculosis .


We found a constitutive degradation of I kappa B-alpha , the major cytoplasmic inhibitor of nuclear factor kappa B ( NF-kappa B ) , in freshly isolated PBMC and monocytes from patients with tuberculosis .

We found a constitutive degradation of <protein>I kappa B-alpha</protein> , the major <protein>cytoplasmic inhibitor</protein> of <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) , in freshly isolated <cell_type>PBMC</cell_type> and <cell_type>monocytes</cell_type> from patients with tuberculosis .


In contrast , I kappa B-alpha levels in PBMC and monocytes from healthy subjects or from patients with nontuberculous pulmonary conditions were intact .

In contrast , <protein>I kappa B-alpha</protein> levels in <cell_type>PBMC</cell_type> and <cell_type>monocytes</cell_type> from healthy subjects or from patients with nontuberculous pulmonary conditions were intact .


Further , by electrophoretic mobility shift assay , NF-kappa B was activated in monocytes from tuberculous patients .

Further , by electrophoretic mobility shift assay , <protein>NF-kappa B</protein> was activated in <cell_type>monocytes</cell_type> from tuberculous patients .


The expression of I kappa B-alpha gene , which is responsive to activation by NF-kappa B , was up-regulated in PBMC and monocytes from patients , but not in mononuclear cells from healthy subjects or those with nontuberculous lung diseases .

The expression of <protein>I kappa B-alpha</protein> gene , which is responsive to activation by <protein>NF-kappa B</protein> , was up-regulated in <cell_type>PBMC</cell_type> and <cell_type>monocytes</cell_type> from patients , but not in <cell_type>mononuclear cells</cell_type> from healthy subjects or those with nontuberculous lung diseases .


By contrast , the expression of other adherence-associated early genes , such as IL-8 and IL-1 beta , was not up-regulated in PBMC of tuberculous patients .

By contrast , the expression of other <dna>adherence-associated early genes</dna> , such as <protein>IL-8</protein> and <protein>IL-1 beta</protein> , was not up-regulated in <cell_type>PBMC</cell_type> of tuberculous patients .


Further , M. tuberculosis and its tuberculin , purified protein derivative , induced the degradation of I kappa B-alpha and the expression of I kappa B-alpha mRNA , and purified protein derivative induced the activation of NF-kappa B in monocytes .

Further , M. tuberculosis and its <protein>tuberculin</protein> , <protein>purified protein derivative</protein> , induced the degradation of <protein>I kappa B-alpha</protein> and the expression of <rna>I kappa B-alpha mRNA</rna> , and purified protein derivative induced the activation of <protein>NF-kappa B</protein> in <cell_type>monocytes</cell_type> .


Cooperation of Spi-1/PU.1 with an activated erythropoietin receptor inhibits apoptosis and Epo -dependent differentiation in primary erythroblasts and induces their Kit ligand-dependent proliferation .

Cooperation of <protein>Spi-1/PU.1</protein> with an <protein>activated erythropoietin receptor</protein> inhibits apoptosis and <protein>Epo</protein> -dependent differentiation in <cell_type>primary erythroblasts</cell_type> and induces their Kit ligand-dependent proliferation .


Spi-1/PU.1 is a myeloid- and B-cell specific transcription factor which is also involved in Friend virus-induced murine erythroleukemia .

<protein>Spi-1/PU.1</protein> is a <protein>myeloid- and B-cell specific transcription factor</protein> which is also involved in Friend virus-induced murine erythroleukemia .


The pre-leukemic phase of Friend erythroleukemia results from activation of the erythropoietin receptor ( EpoR ) by the spleen focus forming virus ( SFFV ) envelope glycoprotein , followed by the emergence of leukemic clones characterized by overexpression of Spi-1 and mutation of the p53 tumor suppressor gene .

The pre-leukemic phase of Friend erythroleukemia results from activation of the <protein>erythropoietin receptor</protein> ( <protein>EpoR</protein> ) by the <protein>spleen focus forming virus ( SFFV ) envelope glycoprotein</protein> , followed by the emergence of leukemic clones characterized by overexpression of <protein>Spi-1</protein> and mutation of the <dna>p53 tumor suppressor gene</dna> .


We developed a heterologous system to analyze the contribution of these alterations to the induction of primary erythroblast transformation .


Avian erythroblasts expressing the activated mouse EpoR ( R129C ) differentiated into erythrocytes in response to hEpo .

<cell_type>Avian erythroblasts</cell_type> expressing the <protein>activated mouse EpoR ( R129C )</protein> differentiated into <cell_type>erythrocytes</cell_type> in response to <protein>hEpo</protein> .


Expression of Spi-1 in these cells inhibited this ability to differentiate and rescued the cells from the apoptotic cell death program normally induced upon hEpo withdrawal .

Expression of <protein>Spi-1</protein> in these cells inhibited this ability to differentiate and rescued the cells from the apoptotic cell death program normally induced upon <protein>hEpo</protein> withdrawal .


Although devoid of any effect by itself , a mutant p53 cooperated with Spi-1 and EpoR ( R129C ) to reinforce both phenotypes .

Although devoid of any effect by itself , a <protein>mutant p53</protein> cooperated with <protein>Spi-1</protein> and <protein>EpoR ( R129C )</protein> to reinforce both phenotypes .


Analysis of erythroblasts co-expressing Spi-1 and the wild-type mouse EpoR showed that differentiation arrest and inhibition of apoptosis depended on specific cooperation between Spi-1 and EpoR ( R129C ) .

Analysis of erythroblasts co-expressing <protein>Spi-1</protein> and the <protein>wild-type mouse EpoR</protein> showed that differentiation arrest and inhibition of apoptosis depended on specific cooperation between <protein>Spi-1</protein> and <protein>EpoR ( R129C )</protein> .


This cooperation was also required to induce the sustained proliferation of differentiation-blocked erythroblasts in response to ligand activation of the endogenous tyrosine kinase receptor c-Kit .

This cooperation was also required to induce the sustained proliferation of <cell_line>differentiation-blocked erythroblasts</cell_line> in response to ligand activation of the <protein>endogenous tyrosine kinase receptor</protein> <protein>c-Kit</protein> .


These results show that Spi-1/ PU.1 requires signals emanating from specific cytokine and growth factor receptors to affect the survival , proliferation and differentiation control of primary erythroblasts .

These results show that Spi-1/ <protein>PU.1</protein> requires signals emanating from specific cytokine and growth factor receptors to affect the survival , proliferation and differentiation control of <cell_type>primary erythroblasts</cell_type> .


They also suggest that the function of Spi-1/PU.1 in the late phase of Friend leukemia requires specific signaling from the gp55-modified EpoR generated during the early phase of the disease .

They also suggest that the function of <protein>Spi-1/PU.1</protein> in the late phase of Friend leukemia requires specific signaling from the <protein>gp55-modified EpoR</protein> generated during the early phase of the disease .


The role of Rel/NF-kappa B proteins in viral oncogenesis and the regulation of viral transcription .

The role of <protein>Rel/NF-kappa B proteins</protein> in viral oncogenesis and the regulation of viral transcription .


Rel/NF-kappa B is a ubiquitous transcription factor that consists of multiple polypeptide subunits , and is subject to complex regulatory mechanisms that involve protein-protein interactions , phosphorylation , ubiquitination , proteolytic degradation , and nucleocytoplasmic translocation .

<protein>Rel/NF-kappa B</protein> is a <protein>ubiquitous transcription factor</protein> that consists of <protein>multiple polypeptide subunits</protein> , and is subject to complex regulatory mechanisms that involve protein-protein interactions , phosphorylation , ubiquitination , proteolytic degradation , and nucleocytoplasmic translocation .


The sophisticated control of Rel/NF-kappa B activity is not surprising since this transcription factor is involved in a wide array of cellular responses to extracellular cues , associated with growth , development , apoptosis , and pathogen invasion .

The sophisticated control of <protein>Rel/NF-kappa B</protein> activity is not surprising since this <protein>transcription factor</protein> is involved in a wide array of cellular responses to extracellular cues , associated with growth , development , apoptosis , and pathogen invasion .


Thus , it is not unexpected that this versatile cellular homeostatic switch would be affected by a variety of viral pathogens , which have evolved mechanisms to utilize various aspects of Rel/NF-kappa B activity to facilitate their replication , cell survival and possibly evasion of immune responses .

Thus , it is not unexpected that this versatile cellular homeostatic switch would be affected by a variety of viral pathogens , which have evolved mechanisms to utilize various aspects of <protein>Rel/NF-kappa B</protein> activity to facilitate their replication , cell survival and possibly evasion of immune responses .


This review will cover the molecular mechanisms that are utilized by mammalian oncogenic viruses to affect the activity of Rel/NF-kappa B transcription factors and the role of Rel/NF-kappa B in the regulation of viral gene expression and replication .

This review will cover the molecular mechanisms that are utilized by mammalian oncogenic viruses to affect the activity of <protein>Rel/NF-kappa B</protein> <protein>transcription factors</protein> and the role of <protein>Rel/NF-kappa B</protein> in the regulation of viral gene expression and replication .


Cellular and molecular mechanisms of IL-5 synthesis in atopic diseases : a study with allergen-specific human helper T cells .

Cellular and molecular mechanisms of <protein>IL-5</protein> synthesis in atopic diseases : a study with <cell_line>allergen-specific human helper T cells</cell_line> .


BACKGROUND : Cytokines produced by helper T cells are intimately involved in chronic allergic diseases associated with eosinophilic inflammation .

BACKGROUND : <protein>Cytokines</protein> produced by <cell_type>helper T cells</cell_type> are intimately involved in chronic allergic diseases associated with eosinophilic inflammation .


OBJECTIVE : We investigated the production of IL-5 , a potent growth factor and chemotactic factor for eosinophils , by CD4+ T lymphocytes in patients with asthma .

OBJECTIVE : We investigated the production of <protein>IL-5</protein> , a potent growth factor and chemotactic factor for <cell_type>eosinophils</cell_type> , by <cell_type>CD4+ T lymphocytes</cell_type> in patients with asthma .


METHODS : Allergen-specific T cell clones and T cell hybridomas were established from the peripheral blood lymphocytes of patients with asthma , and the responses to various stimuli were determined .

METHODS : <cell_line>Allergen-specific T cell clones</cell_line> and <cell_line>T cell hybridomas</cell_line> were established from the <cell_type>peripheral blood lymphocytes</cell_type> of patients with asthma , and the responses to various stimuli were determined .


RESULTS : After nonspecific stimulation , IL-5 production by CD4+ T cells from both atopic and nonatopic subjects with asthma was significantly enhanced compared with that by cells from healthy controls .

RESULTS : After nonspecific stimulation , <protein>IL-5</protein> production by <cell_type>CD4+ T cells</cell_type> from both atopic and nonatopic subjects with asthma was significantly enhanced compared with that by cells from healthy controls .


Peripheral blood mononuclear cells from atopic asthma patients both proliferated and produced IL-5 after incubation with mite allergen , suggesting that mite-specific helper T cells were involved in the eosinophilic inflammation of atopic asthma .

<cell_type>Peripheral blood mononuclear cells</cell_type> from atopic asthma patients both proliferated and produced <protein>IL-5</protein> after incubation with mite allergen , suggesting that <cell_type>mite-specific helper T cells</cell_type> were involved in the eosinophilic inflammation of atopic asthma .


A human IL-5 promoter/enhancer luciferase gene construct transfected into IL-5-producing T cell clones was clearly transcribed after stimulation , indicating that the 515 base pair IL-5 gene segment upstream of the coding region was sufficient to respond to activating signals in human helper T cells .

A human <dna>IL-5 promoter/enhancer luciferase gene construct</dna> transfected into <cell_line>IL-5-producing T cell clones</cell_line> was clearly transcribed after stimulation , indicating that the 515 base pair <dna>IL-5 gene segment</dna> upstream of the coding region was sufficient to respond to activating signals in human <cell_type>helper T cells</cell_type> .


The same gene segment was not transcribed in IL-5-nonproducing T cell clones , suggesting that human T cell IL-5 synthesis is regulated at the transcriptional level .

The same gene segment was not transcribed in <cell_line>IL-5-nonproducing T cell clones</cell_line> , suggesting that human T cell <protein>IL-5</protein> synthesis is regulated at the transcriptional level .


Experiments with T cell hybridomas confirmed these findings and suggested that a unique transcription factor may be essential for human IL-5 gene transcription .

Experiments with <cell_line>T cell hybridomas</cell_line> confirmed these findings and suggested that a <protein>unique transcription factor</protein> may be essential for human <protein>IL-5</protein> gene transcription .


CONCLUSION : Enhanced IL-5 production by helper T cells seems to cause the eosinophilic inflammation of both atopic and nonatopic asthma .

CONCLUSION : Enhanced <protein>IL-5</protein> production by <cell_type>helper T cells</cell_type> seems to cause the eosinophilic inflammation of both atopic and nonatopic asthma .


Elucidation of IL-5 -specific regulatory mechanisms may facilitate the development of novel treatments for allergic diseases associated with eosinophilic inflammation .

Elucidation of <protein>IL-5</protein> -specific regulatory mechanisms may facilitate the development of novel treatments for allergic diseases associated with eosinophilic inflammation .


Cyclosporin A inhibits monocyte tissue factor activation in cardiac transplant recipients .

Cyclosporin A inhibits monocyte <protein>tissue factor</protein> activation in cardiac transplant recipients .


BACKGROUND : Fibrin deposition and thrombosis have been implicated in both allograft rejection and vasculopathy after cardiac transplantation .


Because monocytes play a pivotal role in the pathophysiology of intravascular coagulation activation through their ability to synthesize tissue factor ( TF ) , we asked ( 1 ) whether monocyte TF activation occurs in cardiac transplant recipients and ( 2 ) whether monocyte TF expression is affected by treatment with cyclosporin A ( CsA ) .

Because <cell_type>monocytes</cell_type> play a pivotal role in the pathophysiology of intravascular coagulation activation through their ability to synthesize <protein>tissue factor</protein> ( <protein>TF</protein> ) , we asked ( 1 ) whether monocyte <protein>TF</protein> activation occurs in cardiac transplant recipients and ( 2 ) whether monocyte <protein>TF</protein> expression is affected by treatment with cyclosporin A ( CsA ) .


METHODS AND RESULTS : We measured levels of TF activity in peripheral blood mononuclear cells and highly purified monocytes/macrophages from 10 consecutive cardiac transplant recipients and 10 healthy control subjects .

METHODS AND RESULTS : We measured levels of <protein>TF</protein> activity in <cell_type>peripheral blood mononuclear cells</cell_type> and <cell_type>highly purified monocytes/macrophages</cell_type> from 10 consecutive cardiac transplant recipients and 10 healthy control subjects .


TF activity generated by both unstimulated and endotoxin-stimulated cells was significantly higher in transplant recipients than in control subjects ( P < .05 ) .

<protein>TF</protein> activity generated by both <cell_line>unstimulated</cell_line> and <cell_line>endotoxin-stimulated cells</cell_line> was significantly higher in transplant recipients than in control subjects ( P < .05 ) .


Increased monocyte TF expression in transplant recipients was shown to be adversely affected by treatment with CsA : TF induction was markedly reduced by CsA serum concentrations reaching peak CsA drug levels .

Increased monocyte <protein>TF</protein> expression in transplant recipients was shown to be adversely affected by treatment with CsA : <protein>TF</protein> induction was markedly reduced by CsA serum concentrations reaching peak CsA drug levels .


Inhibition of TF induction in the presence of high CsA blood concentrations was also observed when stimulation of cells was performed with interferon-gamma or interleukin-1beta .

Inhibition of <protein>TF</protein> induction in the presence of high CsA blood concentrations was also observed when stimulation of cells was performed with <protein>interferon-gamma</protein> or <protein>interleukin-1beta</protein> .


As shown by reverse transcription-polymerase chain reaction and electrophoretic mobility shift assay , respectively , treatment with CsA leads to decreased TF mRNA expression and reduced activation of the NF-kappaB transcription factor , which is known to contribute to the induction of the TF promotor in human monocytes .

As shown by reverse transcription-polymerase chain reaction and electrophoretic mobility shift assay , respectively , treatment with CsA leads to decreased <rna>TF mRNA</rna> expression and reduced activation of the <protein>NF-kappaB transcription factor</protein> , which is known to contribute to the induction of the <dna>TF promotor</dna> in <cell_type>human monocytes</cell_type> .


CONCLUSIONS : This study demonstrates that TF activation , occurring in mononuclear cells of cardiac transplant recipients , is inhibited by treatment with CsA .

CONCLUSIONS : This study demonstrates that <protein>TF</protein> activation , occurring in <cell_type>mononuclear cells</cell_type> of cardiac transplant recipients , is inhibited by treatment with CsA .


Inhibition of monocyte TF induction by CsA may contribute to its successful use in cardiac transplant medicine and might be useful in managing further settings of vascular pathology also known to involve TF expression and NF-kappaB activation .

Inhibition of monocyte <protein>TF</protein> induction by CsA may contribute to its successful use in cardiac transplant medicine and might be useful in managing further settings of vascular pathology also known to involve <protein>TF</protein> expression and <protein>NF-kappaB</protein> activation .


IL-2 and IL-7 induce heterodimerization of STAT5 isoforms in human peripheral blood T lymphoblasts .

<protein>IL-2</protein> and <protein>IL-7</protein> induce heterodimerization of <protein>STAT5 isoforms</protein> in <cell_type>human peripheral blood T lymphoblasts</cell_type> .


Despite differences in T cell responses induced by interleukin ( IL ) -2 and IL-7 , both cytokines modulate T cell functions by activation of signal transducers and activators of transcription ( STAT ) proteins .

Despite differences in T cell responses induced by <protein>interleukin ( IL ) -2</protein> and <protein>IL-7</protein> , both <protein>cytokines</protein> modulate T cell functions by activation of <protein>signal transducers and activators of transcription ( STAT ) proteins</protein> .


We examined the contribution of the two isoforms of STAT5 , STAT5A and STAT5B , to IL-2- and IL-7-induced activation of human peripheral blood T lymphoblasts .

We examined the contribution of the two isoforms of <protein>STAT5</protein> , <protein>STAT5A</protein> and <protein>STAT5B</protein> , to IL-2- and IL-7-induced activation of <cell_type>human peripheral blood T lymphoblasts</cell_type> .


Both cytokines induced assembly of STAT5A and STAT5B containing complexes capable of binding to the interferon-gamma activation sequence ( GAS ) , and these complexes rapidly translocated ( within 1 min ) into the nucleus of IL-2- or IL-7-treated cells .

Both <protein>cytokines</protein> induced assembly of <protein>STAT5A</protein> and <protein>STAT5B</protein> containing complexes capable of binding to the <dna>interferon-gamma activation sequence</dna> ( <dna>GAS</dna> ) , and these complexes rapidly translocated ( within 1 min ) into the nucleus of <cell_line>IL-2- or IL-7-treated cells</cell_line> .


The kinetics of this translocation were delayed in IL-7-treated as compared to IL-2-treated cells .

The kinetics of this translocation were delayed in <cell_line>IL-7-treated</cell_line> as compared to <cell_line>IL-2-treated cells</cell_line> .


IL-2 and IL-7 were equivalent in their ability to induce tyrosine phosphorylation of STAT5A and STAT5B and to facilitate binding of these STATs to an immobilized GAS element .

<protein>IL-2</protein> and <protein>IL-7</protein> were equivalent in their ability to induce tyrosine phosphorylation of <protein>STAT5A</protein> and <protein>STAT5B</protein> and to facilitate binding of these <protein>STATs</protein> to an <dna>immobilized GAS element</dna> .


Both IL-2 and IL-7 induced substantial amounts of STAT5A /STAT5B heterodimerization .

Both <protein>IL-2</protein> and <protein>IL-7</protein> induced substantial amounts of <protein>STAT5A</protein> <protein>/STAT5B</protein> heterodimerization .


Moreover , we observed constitutive association of STAT3 with each STAT5 isomer .

Moreover , we observed constitutive association of <protein>STAT3</protein> with each <protein>STAT5 isomer</protein> .


These data suggest that IL-2 and IL-7 induce assembly of STAT heterodimers in a similar manner and that subsequent cellular responses may be driven by induction of similar sets of genes .

These data suggest that <protein>IL-2</protein> and <protein>IL-7</protein> induce assembly of <protein>STAT heterodimers</protein> in a similar manner and that subsequent cellular responses may be driven by induction of similar sets of <dna>genes</dna> .


Transcription factor NF-kappaB regulates inducible Oct-2 gene expression in precursor B lymphocytes .

<protein>Transcription factor</protein> <protein>NF-kappaB</protein> regulates inducible <dna>Oct-2 gene</dna> expression in <cell_type>precursor B lymphocytes</cell_type> .


The POU transcription factors Oct-1 and Oct-2 regulate the activity of octamer-dependent promoters , including those that direct transcription from rearranged immunoglobulin genes .

The <protein>POU transcription factors</protein> <protein>Oct-1</protein> and <protein>Oct-2</protein> regulate the activity of <dna>octamer-dependent promoters</dna> , including those that direct transcription from rearranged <protein>immunoglobulin genes</protein> .


Unlike Oct-1 , which is constitutively expressed in many cell types , Oct-2 expression is restricted primarily to B lymphocytes and can be induced in precursor B cells by stimulation with bacterial lipopolysaccharide ( LPS ) .

Unlike <protein>Oct-1</protein> , which is constitutively expressed in many cell types , <protein>Oct-2</protein> expression is restricted primarily to <cell_type>B lymphocytes</cell_type> and can be induced in <cell_type>precursor B cells</cell_type> by stimulation with bacterial lipopolysaccharide ( LPS ) .


However , the precise factors that mediate this induction mechanism remain unknown .


In the present study , we monitored Oct-2 expression in cells arrested for the activation of NF-kappaB , an LPS-responsive member of the Rel transcription factor family .

In the present study , we monitored <protein>Oct-2</protein> expression in cells arrested for the activation of <protein>NF-kappaB</protein> , an <protein>LPS-responsive member</protein> of the <protein>Rel transcription factor family</protein> .


Despite stimulation with LPS , disruption of the NF-kappaB signaling pathway in precursor B cells led to the loss of inducible Oct-2 DNA binding activity in vitro and the suppression of Oct-2 -directed transcription in vivo .

Despite stimulation with LPS , disruption of the <protein>NF-kappaB</protein> signaling pathway in <cell_type>precursor B cells</cell_type> led to the loss of inducible <protein>Oct-2</protein> DNA binding activity in vitro and the suppression of <protein>Oct-2</protein> -directed transcription in vivo .


This biochemical defect correlated with a specific block to Oct-2 gene expression at the level of transcription , whereas the expression of Oct-1 was unaffected .

This biochemical defect correlated with a specific block to <dna>Oct-2 gene</dna> expression at the level of transcription , whereas the expression of <protein>Oct-1</protein> was unaffected .


The finding that Oct-2 is under NF-kappaB control highlights an important cross-talk mechanism involving two distinct transcription factor families that regulate B lymphocyte function .

The finding that <protein>Oct-2</protein> is under <protein>NF-kappaB</protein> control highlights an important cross-talk mechanism involving two distinct <protein>transcription factor families</protein> that regulate <cell_type>B lymphocyte</cell_type> function .


Suppression of MHC class II expression by human class II trans-activator constructs lacking the N-terminal domain .

Suppression of <protein>MHC class II</protein> expression by <dna>human class II trans-activator constructs</dna> lacking the <protein>N-terminal domain</protein> .


The class II trans-activator ( CIITA ) is a bi- or multi-functional domain protein which plays a critical role in the expression of MHC class II genes .

The <protein>class II trans-activator</protein> ( <protein>CIITA</protein> ) is a <protein>bi- or multi-functional domain protein</protein> which plays a critical role in the expression of <dna>MHC class II genes</dna> .


We report that removal of the N-terminal 151 amino acids , encompassing all of the acidic domain but leaving intact the proline/serine/threonine-rich domain , results in a mutant protein with potent suppressive properties for MHC class II expression .

We report that removal of the <protein>N-terminal 151 amino acids</protein> , encompassing all of the <protein>acidic domain</protein> but leaving intact the <protein>proline/serine/threonine-rich domain</protein> , results in a mutant protein with potent suppressive properties for <protein>MHC class II</protein> expression .


HeLa cells stably or transiently transfected with mutant CIITA constructs showed up to 99 % suppression of MHC class II antigen induction by IFN-gamma and marked suppression of HLA-DRA mRNA expression .

<cell_line>HeLa cells</cell_line> stably or transiently transfected with <dna>mutant CIITA constructs</dna> showed up to 99 % suppression of <protein>MHC class II</protein> antigen induction by <protein>IFN-gamma</protein> and marked suppression of <rna>HLA-DRA mRNA</rna> expression .


Transient transfection of a B lymphoma line resulted in up to 89 % reduction of constitutive MHC class II expression within 5 days and suppression of HLA-DRA mRNA synthesis .

Transient transfection of a B lymphoma line resulted in up to 89 % reduction of constitutive <protein>MHC class II</protein> expression within 5 days and suppression of <rna>HLA-DRA mRNA</rna> synthesis .


Helenalin , an anti-inflammatory sesquiterpene lactone from Arnica , selectively inhibits transcription factor NF-kappaB [ see comments ]

Helenalin , an anti-inflammatory sesquiterpene lactone from Arnica , selectively inhibits <protein>transcription factor</protein> <protein>NF-kappaB</protein> [ see comments ]


Alcoholic extracts prepared form Arnicae flos , the collective name for flowerheads from Arnica montana and A. chamissonis ssp. foliosa , are used therapeutically as anti-inflammatory remedies .


The active ingredients mediating the pharmacological effect are mainly sesquiterpene lactones , such as helenalin , 11alpha , 13-dihydrohelenalin , chamissonolid and their ester derivatives .


While these compounds affect various cellular processes , current data do not fully explain how sesquiterpene lactones exert their anti-inflammatory effect .


We show here that helenalin , and , to a much lesser degree , 11alpha , 13-dihydrohelenalin and chamissonolid , inhibit activation of transcription factor NF-kappaB .

We show here that helenalin , and , to a much lesser degree , 11alpha , 13-dihydrohelenalin and chamissonolid , inhibit activation of <protein>transcription factor</protein> <protein>NF-kappaB</protein> .


This difference in efficacy , which correlates with the compounds ' anti-inflammatory potency in vivo , may be explained by differences in structure and conformation .


NF-kappaB , which resides in an inactive , cytoplasmic complex in unstimulated cells , is activated by phosphorylation and degradation of its inhibitory subunit , IkappaB .

<protein>NF-kappaB</protein> , which resides in an inactive , <protein>cytoplasmic complex</protein> in <cell_line>unstimulated cells</cell_line> , is activated by phosphorylation and degradation of its <protein>inhibitory subunit</protein> , <protein>IkappaB</protein> .


Helenalin inhibits NF-kappaB activation in response to four different stimuli in T-cells , B-cells and epithelial cells and abrogates kappaB -driven gene expression .

Helenalin inhibits <protein>NF-kappaB</protein> activation in response to four different stimuli in <cell_type>T-cells</cell_type> , <cell_type>B-cells</cell_type> and <cell_type>epithelial cells</cell_type> and abrogates <protein>kappaB</protein> -driven gene expression .


This inhibition is selective , as the activity of four other transcription factors , Oct-1 , TBP , Sp1 and STAT 5 was not affected .

This inhibition is selective , as the activity of four other <protein>transcription factors</protein> , <protein>Oct-1</protein> , <protein>TBP</protein> , <protein>Sp1</protein> and <protein>STAT 5</protein> was not affected .


We show that inhibition is not due to a direct modification of the active NF-kappaB heterodimer .

We show that inhibition is not due to a direct modification of the active <protein>NF-kappaB heterodimer</protein> .


Rather , helenalin modifies the NF-kappaB/IkappaB complex , preventing the release of IkappaB .

Rather , helenalin modifies the <protein>NF-kappaB/IkappaB complex</protein> , preventing the release of <protein>IkappaB</protein> .


These data suggest a molecular mechanism for the anti-inflammatory effect of sesquiterpene lactones , which differs from that of other nonsteroidal anti-inflammatory drugs ( NSAIDs ) , indomethacin and acetyl salicylic acid .


The tax protein of human T-cell leukemia virus type 1 mediates the transactivation of the c-sis/platelet-derived growth factor-B promoter through interactions with the zinc finger transcription factors Sp1 and NGFI-A/Egr-1 .

The <protein>tax protein</protein> of human T-cell leukemia virus type 1 mediates the transactivation of the <dna>c-sis/platelet-derived growth factor-B promoter</dna> through interactions with the <protein>zinc finger transcription factors</protein> <protein>Sp1</protein> and <protein>NGFI-A/Egr-1</protein> .


Transcriptional up-regulation of the c-sis/platelet-derived growth factor-B ( PDGF-B ) proto-oncogene by the Tax protein of human T-cell leukemia virus type 1 has been implicated as one possible mechanism of cellular transformation by human T-cell leukemia virus type 1 .

Transcriptional up-regulation of the <dna>c-sis/platelet-derived growth factor-B ( PDGF-B ) proto-oncogene</dna> by the <protein>Tax protein</protein> of human T-cell leukemia virus type 1 has been implicated as one possible mechanism of cellular transformation by human T-cell leukemia virus type 1 .


In previous work , we identified an essential site in the c-sis/PDGF-B promoter , Tax-responsive element 1 ( TRE1 ) , necessary for transactivation by Tax .

In previous work , we identified an essential site in the <dna>c-sis/PDGF-B promoter</dna> , <dna>Tax-responsive element 1</dna> ( <dna>TRE1</dna> ) , necessary for transactivation by <protein>Tax</protein> .


We also identified Sp1 , Sp3 , and NGFI-A/Egr-1 as the primary nuclear transcription factors binding to TRE1 which mediate Tax responsiveness .

We also identified <protein>Sp1</protein> , Sp3 , and <protein>NGFI-A/Egr-1</protein> as the <protein>primary nuclear transcription factors</protein> binding to <dna>TRE1</dna> which mediate <protein>Tax</protein> responsiveness .


In the present work , we have investigated the mechanism ( s ) whereby Tax transactivates the c-sis/PDGF-B proto-oncogene .

In the present work , we have investigated the mechanism ( s ) whereby <protein>Tax</protein> transactivates the <dna>c-sis/PDGF-B proto-oncogene</dna> .


In vitro transcription assays showed that Tax was able to significantly increase the transcriptional activity of a template containing the -257 to +74 region of the c-sis/PDGF-B promoter .

In vitro transcription assays showed that <protein>Tax</protein> was able to significantly increase the transcriptional activity of a template containing the <dna>-257 to +74 region</dna> of the <dna>c-sis/PDGF-B promoter</dna> .


Electrophoretic mobility shift assay analysis showed that Tax increased the DNA binding activity of both Sp1 and NGFI-A/Egr-1 using a TRE1 probe .

Electrophoretic mobility shift assay analysis showed that <protein>Tax</protein> increased the DNA binding activity of both <protein>Sp1</protein> and <protein>NGFI-A/Egr-1</protein> using a <dna>TRE1 probe</dna> .


Analysis of Tax mutants showed that two mutants , IEXC29S and IEXL320G , were unable to significantly transactivate the c-sis/PDGF-B promoter .

Analysis of <protein>Tax mutants</protein> showed that two mutants , <protein>IEXC29S</protein> and <protein>IEXL320G</protein> , were unable to significantly transactivate the <dna>c-sis/PDGF-B promoter</dna> .


Finally , co-immunoprecipitation analysis revealed that Tax is able to stably bind to both Sp1 and NGFI-A/Egr-1 .

Finally , co-immunoprecipitation analysis revealed that <protein>Tax</protein> is able to stably bind to both <protein>Sp1</protein> and <protein>NGFI-A/Egr-1</protein> .


Interestingly , co-immunoprecipitation analysis also revealed that Tax mutant IEXC29S is unable to interact with NGFI-A/Egr-1 , whereas Tax mutant IEXL320G is able to interact with NGFI-A/Egr-1 .

Interestingly , co-immunoprecipitation analysis also revealed that <protein>Tax</protein> mutant <protein>IEXC29S</protein> is unable to interact with <protein>NGFI-A/Egr-1</protein> , whereas <protein>Tax</protein> mutant <protein>IEXL320G</protein> is able to interact with <protein>NGFI-A/Egr-1</protein> .


Nuclear localization of RelB is associated with effective antigen-presenting cell function .

Nuclear localization of <protein>RelB</protein> is associated with effective antigen-presenting cell function .


Dendritic cells ( DC ) are potent APCs that enter resting tissues as precursors and , after Ag exposure , differentiate and migrate to draining lymph nodes .

<cell_type>Dendritic cells</cell_type> ( <cell_type>DC</cell_type> ) are potent <cell_type>APCs</cell_type> that enter resting tissues as precursors and , after Ag exposure , differentiate and migrate to draining lymph nodes .


The phenotype of RelB knockout mice implicates this member of the NF kappa B/Rel family in DC differentiation .

The phenotype of <protein>RelB</protein> knockout mice implicates this member of the <protein>NF kappa B/Rel family</protein> in <cell_type>DC</cell_type> differentiation .


To further elucidate the role of RelB in DC differentiation , mRNA , intracellular protein expression , and DNA binding activity of RelB were examined in immature and differentiated human DC , as well as other PB mononuclear cell populations .

To further elucidate the role of <protein>RelB</protein> in <cell_type>DC</cell_type> differentiation , <rna>mRNA</rna> , intracellular protein expression , and DNA binding activity of <protein>RelB</protein> were examined in immature and differentiated <cell_type>human DC</cell_type> , as well as other <cell_type>PB mononuclear cell populations</cell_type> .


RelB protein and mRNA were detected constitutively in lymphocytes and in activated monocytes , differentiated DC , and monocyte-derived DC .

<protein>RelB</protein> protein and <rna>mRNA</rna> were detected constitutively in <cell_type>lymphocytes</cell_type> and in <cell_type>activated monocytes</cell_type> , <cell_type>differentiated DC</cell_type> , and <cell_line>monocyte-derived DC</cell_line> .


Immunohistochemical staining demonstrated RelB within the differentiated lymph node interdigitating DC and follicular DC , but not undifferentiated DC in normal skin .

Immunohistochemical staining demonstrated <protein>RelB</protein> within the <cell_type>differentiated lymph node interdigitating DC</cell_type> and <cell_type>follicular DC</cell_type> , but not <cell_type>undifferentiated DC</cell_type> in normal skin .


Active nuclear RelB was detected by supershift assay only in differentiated DC derived from either PB precursors or monocytes and in activated B cells .

Active nuclear <protein>RelB</protein> was detected by supershift assay only in differentiated <cell_type>DC</cell_type> derived from either <cell_type>PB precursors</cell_type> or <cell_type>monocytes</cell_type> and in <cell_type>activated B cells</cell_type> .


These RelB+ APC were potent stimulators of the MLR .

These <cell_type>RelB+ APC</cell_type> were potent stimulators of the <protein>MLR</protein> .


The data indicate that RelB expression is regulated both transcriptionally and post-translationally in myeloid cells .

The data indicate that <protein>RelB</protein> expression is regulated both transcriptionally and post-translationally in <cell_type>myeloid cells</cell_type> .


Within the nucleus , RelB may specifically transactivate genes that are critical for APC function .

Within the nucleus , <protein>RelB</protein> may specifically transactivate genes that are critical for <cell_type>APC</cell_type> function .


NF-AT activation induced by a CAML -interacting member of the tumor necrosis factor receptor superfamily .

<protein>NF-AT</protein> activation induced by a <protein>CAML</protein> -interacting member of the <protein>tumor necrosis factor receptor superfamily</protein> .


Activation of the nuclear factor of activated T cells transcription factor ( NF-AT ) is a key event underlying lymphocyte action .

Activation of the <protein>nuclear factor of activated T cells</protein> <protein>transcription factor</protein> ( <protein>NF-AT</protein> ) is a key event underlying lymphocyte action .


The CAML ( calcium-modulator and cyclophilin ligand ) protein is a coinducer of NF-AT activation when overexpressed in Jurkat T cells .

The <protein>CAML ( calcium-modulator and cyclophilin ligand ) protein</protein> is a coinducer of <protein>NF-AT</protein> activation when overexpressed in <cell_line>Jurkat T cells</cell_line> .


A member of the tumor necrosis factor receptor superfamily was isolated by virtue of its affinity for CAML .

A member of the <protein>tumor necrosis factor receptor superfamily</protein> was isolated by virtue of its affinity for <protein>CAML</protein> .


Cross-linking of this lymphocyte-specific protein , designated TACI ( transmembrane activator and CAML-interactor ) , on the surface of transfected Jurkat cells with TACI-specific antibodies led to activation of the transcription factors NF-AT , AP-1 , and NFkappaB .

Cross-linking of this <protein>lymphocyte-specific protein</protein> , designated <protein>TACI</protein> ( <protein>transmembrane activator and CAML-interactor</protein> ) , on the surface of <cell_line>transfected Jurkat cells</cell_line> with <protein>TACI-specific antibodies</protein> led to activation of the <protein>transcription factors</protein> <protein>NF-AT</protein> , <protein>AP-1</protein> , and <protein>NFkappaB</protein> .


TACI -induced activation of NF-AT was specifically blocked by a dominant-negative CAML mutant , thus implicating CAML as a signaling intermediate .

<protein>TACI</protein> -induced activation of <protein>NF-AT</protein> was specifically blocked by a <protein>dominant-negative CAML mutant</protein> , thus implicating <protein>CAML</protein> as a signaling intermediate .


Rel/NF-kappa B transcription factors and the control of apoptosis .

<protein>Rel/NF-kappa B</protein> <protein>transcription factors</protein> and the control of apoptosis .


The process of apoptosis is used to eliminate unwanted cells from a wide variety of organisms .

The process of apoptosis is used to eliminate <cell_type>unwanted cells</cell_type> from a wide variety of organisms .


Various extracellular signals , often converging in common intracellular pathways , can induce apoptosis in a cell-type-specific fashion .


Recent work from several laboratories has demonstrated that Rel/NF-kappa B transcription factors regulate apoptosis in many cell types .

Recent work from several laboratories has demonstrated that <protein>Rel/NF-kappa B</protein> <protein>transcription factors</protein> regulate apoptosis in many cell types .


In most cells , Rel/NF-kappa B transcription factors appear to mediate survival signals that protect cells from apoptosis ; however , under some circumstances , activation of these factors may also promote apoptosis .

In most cells , <protein>Rel/NF-kappa B</protein> <protein>transcription factors</protein> appear to mediate survival signals that protect cells from apoptosis ; however , under some circumstances , activation of these factors may also promote apoptosis .


A thiol antioxidant regulates IgE isotype switching by inhibiting activation of nuclear factor-kappaB .

A thiol antioxidant regulates <protein>IgE isotype</protein> switching by inhibiting activation of <protein>nuclear factor-kappaB</protein> .


The binding site for nuclear factor-kappaB ( NF-kappaB ) is present at the promoter region of the germline Cepsilon gene , but there is little information on whether this factor is involved in regulating IgE synthesis by human B cells .

The <dna>binding site</dna> for <protein>nuclear factor-kappaB</protein> ( <protein>NF-kappaB</protein> ) is present at the <dna>promoter region</dna> of the <dna>germline Cepsilon gene</dna> , but there is little information on whether this factor is involved in regulating <protein>IgE</protein> synthesis by <cell_type>human B cells</cell_type> .


Accordingly , we studied the role of NF-kappaB in germline Cepsilon transcription by using two human Burkitt 's lymphoma B cell lines , DND39 and DG75 .

Accordingly , we studied the role of <protein>NF-kappaB</protein> in <dna>germline</dna> Cepsilon transcription by using two <cell_line>human Burkitt 's lymphoma B cell lines</cell_line> , <cell_line>DND39</cell_line> and <cell_line>DG75</cell_line> .


In both cell lines , n-acetyl-L-cysteine ( NAC ) , a potent thiol antioxidant , inhibited the triggering of the nuclear expression of NF-kappaB by IL-4 and by anti-CD40 monoclonal antibody .

In both <cell_line>cell lines</cell_line> , n-acetyl-L-cysteine ( NAC ) , a potent thiol antioxidant , inhibited the triggering of the nuclear expression of <protein>NF-kappaB</protein> by <protein>IL-4</protein> and by <protein>anti-CD40 monoclonal antibody</protein> .


Although IL-4 activated signal transducers and activators of transcription ( STAT ) 6 in addition to NF-kappaB , NAC treatment or the transfection of decoy oligodeoxynucleotides for NF-kappaB or STAT6 only partly blocked IL-4 -induced germline Cepsilon transcription .

Although <protein>IL-4</protein> activated <protein>signal transducers and activators of transcription ( STAT ) 6</protein> in addition to <protein>NF-kappaB</protein> , NAC treatment or the transfection of decoy oligodeoxynucleotides for <protein>NF-kappaB</protein> or <protein>STAT6</protein> only partly blocked <protein>IL-4</protein> -induced <dna>germline</dna> Cepsilon transcription .


However , these two decoy oligodeoxynucleotides together almost completely abrogated IL-4 -induced germline Cepsilon transcription .

However , these two decoy oligodeoxynucleotides together almost completely abrogated <protein>IL-4</protein> -induced <dna>germline</dna> Cepsilon transcription .


Of note , CD40 -mediated enhancement of IL-4 -driven germline Cepsilon transcription was markedly decreased by NAC or by a decoy oligodeoxynucleotide for NF-kappaB .

Of note , <protein>CD40</protein> -mediated enhancement of <protein>IL-4</protein> -driven <dna>germline</dna> Cepsilon transcription was markedly decreased by NAC or by a decoy oligodeoxynucleotide for <protein>NF-kappaB</protein> .


The effect of NAC was also examined on deletional switch recombination underlying the isotype switch to IgE .

The effect of NAC was also examined on deletional switch recombination underlying the isotype switch to <protein>IgE</protein> .


NAC inhibited the generation of Smu/Sepsilon switch fragments in normal human B cells costimulated with IL-4 and anti-CD40 monoclonal antibody .

NAC inhibited the generation of <protein>Smu/Sepsilon switch fragments</protein> in normal <cell_type>human B cells</cell_type> costimulated with <protein>IL-4</protein> and <protein>anti-CD40 monoclonal antibody</protein> .


It also abolished IL-4 -induced upregulation of CD40 but promoted upregulation of CD23 .

It also abolished <protein>IL-4</protein> -induced upregulation of <protein>CD40</protein> but promoted upregulation of CD23 .


These results suggest that coordination of NF-kappaB and STAT6 may be required for induction of germline Cepsilon transcription by IL-4 , and that CD40 -mediated NF-kappaB activation may be important in regulating both enhancement of germline Cepsilon transcription and class switching to IgE .

These results suggest that coordination of <protein>NF-kappaB</protein> and <protein>STAT6</protein> may be required for induction of <dna>germline</dna> Cepsilon transcription by <protein>IL-4</protein> , and that <protein>CD40</protein> -mediated <protein>NF-kappaB</protein> activation may be important in regulating both enhancement of <dna>germline</dna> Cepsilon transcription and class switching to <protein>IgE</protein> .


Pathogenesis .


There are many hypotheses concerning the pathogenesis of endometriosis , though no single theory can explain all cases .


It is likely that several mechanisms are involved .


Early studies concentrated on the histogenesis of the endometriotic lesion .


Recent evidence has implicated components of the immune system in the pathogenesis of endometriosis .


This review considers the evidence for different theories of the histogenesis of endometriosis and discusses possible immune factors that may be involved in the pathophysiology of the disease .


ATF1 and CREB trans-activate a cell cycle regulated histone H4 gene at a distal nuclear matrix associated promoter element .

<protein>ATF1</protein> and <protein>CREB</protein> trans-activate a <dna>cell cycle regulated histone H4 gene</dna> at a <dna>distal nuclear matrix associated promoter element</dna> .


Proteins of the ATF/ CREB class of transcription factors stimulate gene expression of several cell growth-related genes through protein kinase A-related cAMP response elements .

Proteins of the ATF/ <protein>CREB</protein> class of <protein>transcription factors</protein> stimulate gene expression of several <dna>cell growth-related genes</dna> through <dna>protein kinase A-related cAMP response elements</dna> .


The promoter activity of cell cycle regulated histone H4 genes is regulated by at least four principal cis-acting elements which mediate G1/S phase control and/or enhancement of transcription during the cell cycle .

The promoter activity of <dna>cell cycle regulated histone H4 genes</dna> is regulated by at least four <dna>principal cis-acting elements</dna> which mediate G1/S phase control and/or enhancement of transcription during the cell cycle .


Using protein-DNA interaction assays we show that the H4 promoter contains two ATF/ CREB recognition motifs which interact with CREB , ATF1 , and ATF2 but not with ATF4/CREB2 .

Using protein-DNA interaction assays we show that the <dna>H4 promoter</dna> contains two ATF/ <protein>CREB</protein> recognition motifs which interact with <protein>CREB</protein> , <protein>ATF1</protein> , and <protein>ATF2</protein> but not with <protein>ATF4/CREB2</protein> .


One ATF/CRE motif is located in the distal promoter at the nuclear matrix-associated Site IV , and the second motif is present in the proximal promoter at Site I .

One <dna>ATF/CRE motif</dna> is located in the <dna>distal promoter</dna> at the <dna>nuclear matrix-associated Site IV</dna> , and the second motif is present in the <dna>proximal promoter</dna> at <dna>Site I</dna> .


Both ATF/CRE motifs overlap binding sequences for the multifunctional YY1 transcription factor , which has previously been shown to be nuclear matrix associated .

Both <dna>ATF/CRE motifs</dna> overlap <dna>binding sequences</dna> for the <protein>multifunctional YY1 transcription factor</protein> , which has previously been shown to be nuclear matrix associated .


Subnuclear fractionation reveals that there are two ATF1 isoforms which appear to differ with respect to DNA binding activity and partition selectively between nuclear matrix and nonmatrix compartments , consistent with the role of the nuclear matrix in regulating gene expression .

Subnuclear fractionation reveals that there are two <protein>ATF1 isoforms</protein> which appear to differ with respect to DNA binding activity and partition selectively between nuclear matrix and nonmatrix compartments , consistent with the role of the nuclear matrix in regulating gene expression .


Site-directed mutational studies demonstrate that Site I and Site IV together support ATF1- and CREB-induced trans-activation of the H4 promoter .

Site-directed mutational studies demonstrate that <dna>Site I</dna> and <dna>Site IV</dna> together support ATF1- and CREB-induced trans-activation of the <dna>H4 promoter</dna> .


Thus , our data establish that ATF/CREB factors functionally modulate histone H4 gene transcription at distal and proximal promoter elements .

Thus , our data establish that <protein>ATF/CREB factors</protein> functionally modulate <dna>histone H4 gene</dna> transcription at <dna>distal and proximal promoter elements</dna> .


Is celiac disease due to molecular mimicry between gliadin peptide -HLA class II molecule -T cell interactions and those of some unidentified superantigen ?

Is celiac disease due to molecular mimicry between gliadin peptide <protein>-HLA class II molecule</protein> -T cell interactions and those of some <protein>unidentified superantigen</protein> ?


This paper presents a new hypothesis for the etiology and pathogenesis of celiac disease ( CD ) .


It is our contention that CD is triggered by the binding of one or more gliadin peptides to CD-associated HLA class II molecules .

It is our contention that CD is triggered by the binding of one or more gliadin peptides to <protein>CD-associated HLA class II molecules</protein> .


Furthermore , we propose that these putative CD peptides bind to oligosaccharide residues on HLA class II molecules distal to the peptide-binding groove invoking recognition and binding by specialized subsets of gamma delta T cell receptor-bearing lymphocytes .

Furthermore , we propose that these putative CD peptides bind to oligosaccharide residues on <protein>HLA class II molecules</protein> distal to the <protein>peptide-binding groove</protein> invoking recognition and binding by specialized subsets of <cell_type>gamma delta T cell receptor-bearing lymphocytes</cell_type> .


The binding of these gamma delta T cells serves as a signal for abrogation of oral tolerance to ingested proteins setting in motion a series of immune responses directed against the small intestinal epithelium of CD patients .

The binding of these <cell_type>gamma delta T cells</cell_type> serves as a signal for abrogation of oral tolerance to <protein>ingested proteins</protein> setting in motion a series of immune responses directed against the small intestinal epithelium of CD patients .


CD patients are victimized by this self-distructed immune response because of inheritance of certain combinations of HLA-DQ and DR haplotypes .


Dimers encoded by HLA-DR haplotypes may be the primary restriction elements for lectin-like , gliadin peptides while the degree of immune suppression ( or lack thereof ) to ingested gliadins is governed by inherited HLA-DQ haplotypes .

Dimers encoded by <protein>HLA-DR</protein> haplotypes may be the <dna>primary restriction elements</dna> for lectin-like , gliadin peptides while the degree of immune suppression ( or lack thereof ) to ingested gliadins is governed by inherited <dna>HLA-DQ</dna> haplotypes .


Finally , we speculate that molecular mimicry between one or more gliadin peptides and some , as yet unidentified , bacterial or viral superantigen plays a role in disease pathogenesis .

Finally , we speculate that molecular mimicry between one or more gliadin peptides and some , as yet unidentified , <protein>bacterial or viral superantigen</protein> plays a role in disease pathogenesis .


Epstein-Barr virus latent membrane protein-1 triggers AP-1 activity via the c-Jun N-terminal kinase cascade .

Epstein-Barr virus <protein>latent membrane protein-1</protein> triggers <protein>AP-1</protein> activity via the <protein>c-Jun</protein> N-terminal kinase cascade .


The Epstein-Barr virus latent membrane protein-1 ( LMP-1 ) is an integral membrane protein which transforms fibroblasts and is essential for EBV-mediated B-cell immortalization .

The Epstein-Barr virus <protein>latent membrane protein-1</protein> ( <protein>LMP-1</protein> ) is an <protein>integral membrane protein</protein> which transforms <cell_type>fibroblasts</cell_type> and is essential for EBV-mediated B-cell immortalization .


LMP-1 has been shown to trigger cellular NF-kappa B activity which , however , can not fully explain the oncogenic potential of LMP-1 .

<protein>LMP-1</protein> has been shown to trigger cellular <protein>NF-kappa B</protein> activity which , however , can not fully explain the oncogenic potential of <protein>LMP-1</protein> .


Here we show that LMP-1 induces the activity of the AP-1 transcription factor , a dimer of Jun/Jun or Jun/Fos proteins .

Here we show that <protein>LMP-1</protein> induces the activity of the <protein>AP-1 transcription factor</protein> , a dimer of <protein>Jun/Jun or Jun/Fos proteins</protein> .


LMP-1 effects on AP-1 are mediated through activation of the c-Jun N-terminal kinase ( JNK ) cascade , but not the extracellular signal-regulated kinase ( Erk ) pathway .

<protein>LMP-1</protein> effects on <protein>AP-1</protein> are mediated through activation of the <protein>c-Jun</protein> N-terminal kinase ( <protein>JNK</protein> ) cascade , but not the <protein>extracellular signal-regulated kinase</protein> ( <protein>Erk</protein> ) pathway .


Consequently , LMP-1 triggers the activity of the c-Jun N-terminal transactivation domain which is known to be activated upon JNK -mediated phosphorylation .

Consequently , <protein>LMP-1</protein> triggers the activity of the <protein>c-Jun N-terminal transactivation domain</protein> which is known to be activated upon <protein>JNK</protein> -mediated phosphorylation .


Deletion analysis indicates that the 55 C-terminal amino acids of the LMP-1 molecule , but not its TRAF interaction domain , are essential for AP-1 activation .

Deletion analysis indicates that the 55 <protein>C-terminal amino acids</protein> of the <protein>LMP-1 molecule</protein> , but not its <protein>TRAF interaction domain</protein> , are essential for <protein>AP-1</protein> activation .