We now report that galectin-3 is abundantly expressed in a number of human T lymphotropic virus ( HTLV ) -I-infected human T cell lines , including F6T , HUT 102 , K3T , MT-2 , and SLB-I , but is not expressed in non-HTLV-I-infected T cell lines such as Jurkat , CEM , and MOLT-4 .

We now report that <protein>galectin-3</protein> is abundantly expressed in a number of <cell_line>human T lymphotropic virus ( HTLV ) -I-infected human T cell lines</cell_line> , including <cell_line>F6T</cell_line> , <cell_line>HUT 102</cell_line> , <cell_line>K3T</cell_line> , <cell_line>MT-2</cell_line> , and <cell_line>SLB-I</cell_line> , but is not expressed in <cell_line>non-HTLV-I-infected T cell lines</cell_line> such as <cell_line>Jurkat</cell_line> , <cell_line>CEM</cell_line> , and <cell_line>MOLT-4</cell_line> .


In addition , the galectin-3 level was markedly increased in human thymocytes after infection with HTLV-I as compared with uninfected thymocytes .

In addition , the <protein>galectin-3</protein> level was markedly increased in <cell_type>human thymocytes</cell_type> after infection with HTLV-I as compared with <cell_type>uninfected thymocytes</cell_type> .


The up-regulation of galectin-3 expression appeared to correlate well with HTLV-I gene expression , as undetectable or very low levels of galectin-3 were found in the S1T and ATL-1K cell lines , which are nonproductively infected with HTLV-I .

The up-regulation of <protein>galectin-3</protein> expression appeared to correlate well with HTLV-I gene expression , as undetectable or very low levels of <protein>galectin-3</protein> were found in the <cell_line>S1T and ATL-1K cell lines</cell_line> , which are nonproductively infected with HTLV-I .


In co-transfection experiments , the galectin-3 promoter was significantly up-regulated by expression vectors encoding the 40-kd Tax protein , a potent transactivator in HTLV-I .

In co-transfection experiments , the <dna>galectin-3 promoter</dna> was significantly up-regulated by <dna>expression vectors</dna> encoding the <protein>40-kd Tax protein</protein> , a potent transactivator in HTLV-I .


Analysis of various Tax mutants suggested that galectin-3 promoter induction is dependent on activation of the cyclic-AMP-responsive element binding protein/activation transcription factor family of transcription factors and , to a lesser extent , nuclear factor-kappa B/Rel induction .

Analysis of various <protein>Tax mutants</protein> suggested that <dna>galectin-3 promoter</dna> induction is dependent on activation of the <protein>cyclic-AMP-responsive element binding protein/activation transcription factor family</protein> of <protein>transcription factors</protein> and , to a lesser extent , <protein>nuclear factor-kappa B/Rel</protein> induction .


Transfection of human promonocytic U-937 cells with an HTLV-I Tax expression vector induced galectin-3 expression in this cell line .

Transfection of <cell_line>human promonocytic U-937 cells</cell_line> with an HTLV-I Tax expression vector induced <protein>galectin-3</protein> expression in this cell line .


Functionally , galectin-3 was shown to activate interleukin-2 production in Jurkat T cells .

Functionally , <protein>galectin-3</protein> was shown to activate <protein>interleukin-2</protein> production in <cell_type>Jurkat T cells</cell_type> .


Together , these findings raise the possibility that HTLV-I Tax production induces the transcription and subsequent synthesis and secretion of galectin-3 , which in turn may further activate these T cells and contribute to the altered properties of cell growth found in adult T cell leukemia induced by HTLV-I .

Together , these findings raise the possibility that HTLV-I <protein>Tax</protein> production induces the transcription and subsequent synthesis and secretion of <protein>galectin-3</protein> , which in turn may further activate these <cell_type>T cells</cell_type> and contribute to the altered properties of cell growth found in adult T cell leukemia induced by HTLV-I .


Monocytic cell type-specific transcriptional induction of collagenase .

Monocytic cell type-specific transcriptional induction of <protein>collagenase</protein> .


Interstitial collagenase ( MMP-1 ) , a metalloproteinase produced by resident and inflammatory cells during connective tissue turnover , cleaves type I collagen fibrils .

Interstitial <protein>collagenase</protein> ( <protein>MMP-1</protein> ) , a <protein>metalloproteinase</protein> produced by <cell_type>resident and inflammatory cells</cell_type> during connective tissue turnover , cleaves <protein>type I collagen fibrils</protein> .


This catalytic event is rate limiting in remodeling of tissues rich in fibrillar collagen such as the skin and lungs .

This catalytic event is rate limiting in remodeling of tissues rich in <protein>fibrillar collagen</protein> such as the skin and lungs .


The regulation of collagenase expression is cell-type specific ; bacterial LPS and zymosan , a yeast cell wall derivative , are potent inducers of collagenase expression in macrophages , but do not alter fibroblast collagenase expression .

The regulation of <protein>collagenase</protein> expression is cell-type specific ; bacterial LPS and zymosan , a yeast cell wall derivative , are potent inducers of <protein>collagenase</protein> expression in <cell_type>macrophages</cell_type> , but do not alter <cell_type>fibroblast</cell_type> <protein>collagenase</protein> expression .


Since promoter elements controlling collagenase transcription in monocytic cells have not been previously defined , we sought to delineate responsive cis-acting elements of the collagenase promoter in transiently transfected human ( U937 ) and murine ( J774 ) monocytic cell lines .

Since promoter elements controlling <protein>collagenase</protein> transcription in monocytic cells have not been previously defined , we sought to delineate responsive <dna>cis-acting elements</dna> of the <dna>collagenase promoter</dna> in transiently transfected <cell_line>human ( U937 ) and murine ( J774 ) monocytic cell lines</cell_line> .


Deletion constructs containing as little as 72 bp of 5 ' -flanking sequence of the collagenase promoter were sufficient for LPS- or zymosan-mediated transcriptional induction , whereas phorbol inducibility exhibited an absolute requirement for upstream elements including the polyoma enhancer A-binding protein-3 site ( -83 to -91 ) and TTCA sequence ( -102 to -105 ) in both monocytic cells and fibroblasts .

Deletion constructs containing as little as 72 bp of <dna>5 ' -flanking sequence</dna> of the <dna>collagenase promoter</dna> were sufficient for LPS- or zymosan-mediated transcriptional induction , whereas phorbol inducibility exhibited an absolute requirement for upstream elements including the <dna>polyoma enhancer A-binding protein-3 site</dna> ( <dna>-83 to -91</dna> ) and <dna>TTCA sequence</dna> ( <dna>-102 to -105</dna> ) in both <cell_type>monocytic cells</cell_type> and <cell_type>fibroblasts</cell_type> .


Mutagenesis of the activator protein-1 [ AP-1 ] site at -72 abolished basal promoter activity and LPS/zymosan inducibility , while mutagenesis of an NF-kappaB-like site at -20 to -10 had no effect .

Mutagenesis of the <dna>activator protein-1 [ AP-1 ] site</dna> at <dna>-72</dna> abolished <dna>basal promoter</dna> activity and LPS/zymosan inducibility , while mutagenesis of an <dna>NF-kappaB-like site</dna> at -20 to -10 had no effect .


Nuclear extracts from LPS -and zymosan-treated cells showed strong AP-1 activity by gel-shift analysis , and supershift analysis showed the AP-1 complexes contained specific members of both the jun and fos gene families .

Nuclear extracts from LPS -and <cell_type>zymosan-treated cells</cell_type> showed strong <protein>AP-1</protein> activity by gel-shift analysis , and supershift analysis showed the <protein>AP-1 complexes</protein> contained specific members of both the <dna>jun and fos gene families</dna> .


These data indicate that , in contrast to most LPS effects , AP-1 , but not nuclear factor-kappaB , mediates LPS induction of collagenase transcription in macrophagelike cells .

These data indicate that , in contrast to most LPS effects , <protein>AP-1</protein> , but not <protein>nuclear factor-kappaB</protein> , mediates LPS induction of <protein>collagenase</protein> transcription in <cell_type>macrophagelike cells</cell_type> .


Furthermore , as compared to regulation by phorbol ester , collagenase induction in monocytic cells by cell wall derivatives of bacteria or yeast is largely independent of upstream promoter sequences .

Furthermore , as compared to regulation by phorbol ester , <protein>collagenase</protein> induction in <cell_type>monocytic cells</cell_type> by cell wall derivatives of bacteria or yeast is largely independent of <dna>upstream promoter sequences</dna> .


Activation of c-Jun N-terminal kinase in bacterial lipopolysaccharide-stimulated macrophages .

Activation of <protein>c-Jun N-terminal kinase</protein> in <cell_type>bacterial lipopolysaccharide-stimulated macrophages</cell_type> .


Activation of macrophages by bacterial lipopolysaccharide ( LPS ) induces transcription of genes that encode for proinflammatory regulators of the immune response .

Activation of <cell_type>macrophages</cell_type> by bacterial lipopolysaccharide ( LPS ) induces transcription of genes that encode for <protein>proinflammatory regulators</protein> of the immune response .


Previous work has suggested that activation of the transcription factor activator protein 1 ( AP-1 ) is one LPS-induced event that mediates this response .

Previous work has suggested that activation of the <protein>transcription factor activator protein 1</protein> ( <protein>AP-1</protein> ) is one LPS-induced event that mediates this response .


Consistent with this notion , we found that LPS stimulated AP-1 -mediated transcription of a transfected reporter gene in the murine macrophage cell line RAW 264.7 .

Consistent with this notion , we found that LPS stimulated <protein>AP-1</protein> -mediated transcription of a <dna>transfected reporter gene</dna> in the <cell_line>murine macrophage cell line RAW 264.7</cell_line> .


As AP-1 activity is regulated in part by activation of the c-Jun N-terminal kinase ( JNK ) , which phosphorylates and subsequently increases the transcriptional activity of c-Jun , we examined whether LPS treatment of macrophages resulted in activation of this kinase .

As <protein>AP-1</protein> activity is regulated in part by activation of the <protein>c-Jun N-terminal kinase</protein> ( <protein>JNK</protein> ) , which phosphorylates and subsequently increases the transcriptional activity of c-Jun , we examined whether LPS treatment of <cell_type>macrophages</cell_type> resulted in activation of this <protein>kinase</protein> .


LPS treatment of RAW 264.7 cells , murine bone marrow-derived macrophages , and the human monocyte cell line THP-1 resulted in rapid activation of the p46 and p54 isoforms of JNK .

LPS treatment of <cell_line>RAW 264.7 cells</cell_line> , <cell_type>murine bone marrow-derived macrophages</cell_type> , and the <cell_line>human monocyte cell line THP-1</cell_line> resulted in rapid activation of the <protein>p46 and p54 isoforms</protein> of <protein>JNK</protein> .


Treatment with wild-type and rough mutant forms of LPS and synthetic lipid A resulted in JNK activation , while pretreatment with the tyrosine kinase inhibitor herbimycin A inhibited this response .

Treatment with wild-type and rough mutant forms of LPS and synthetic lipid A resulted in <protein>JNK</protein> activation , while pretreatment with the <protein>tyrosine kinase</protein> inhibitor herbimycin A inhibited this response .


Binding of LPS- LPS binding protein ( LBP ) complexes to CD14 , a surface receptor that mediates many LPS responses , was found to be crucial , as pretreatment of THP-1 cells with the monoclonal antibody 60b , which blocks this binding , inhibited JNK activation .

Binding of LPS- <protein>LPS binding protein ( LBP ) complexes</protein> to <protein>CD14</protein> , a <protein>surface receptor</protein> that mediates many LPS responses , was found to be crucial , as pretreatment of <cell_line>THP-1 cells</cell_line> with the <protein>monoclonal antibody 60b</protein> , which blocks this binding , inhibited <protein>JNK</protein> activation .


These results suggest that LPS activation of JNK in monocyte/macrophage cells is a CD14- and protein tyrosine phosphorylation-dependent event that may mediate the early activation of AP-1 in regulating LPS-triggered gene induction .

These results suggest that LPS activation of <protein>JNK</protein> in <cell_type>monocyte/macrophage cells</cell_type> is a CD14- and protein tyrosine phosphorylation-dependent event that may mediate the early activation of <protein>AP-1</protein> in regulating LPS-triggered gene induction .


Surfactant suppresses NF-kappa B activation in human monocytic cells .

Surfactant suppresses <protein>NF-kappa B</protein> activation in human <cell_type>monocytic cells</cell_type> .


In addition to biophysical properties , pulmonary surfactant has immunomodulatory activity .


We previously demonstrated that both synthetic ( Exosurf ) and modified natural surfactant ( Survanta ) downregulated endotoxin-stimulated inflammatory c ytokine mRNA levels and protein products ( tumor necrosis factor-alpha [ TNF ] , interleukin-1-beta [ IL-1 ] , interleukin-6 [ IL-6 ] ) in human alveolar macrophages .

We previously demonstrated that both synthetic ( Exosurf ) and modified natural surfactant ( Survanta ) downregulated endotoxin-stimulated <rna>inflammatory c ytokine mRNA</rna> levels and <protein>protein products</protein> ( <protein>tumor necrosis factor-alpha</protein> [ TNF ] , <protein>interleukin-1-beta</protein> [ <protein>IL-1</protein> ] , <protein>interleukin-6</protein> [ <protein>IL-6</protein> ] ) in <cell_type>human alveolar macrophages</cell_type> .


In this study , we report that both Exosurf and Survanta suppress TNF mRNA and secretion ( 85 +/- 4 % mean percent inhibition +/- SEM by Exosurf ; 71 +/- 6 % by Survanta ) by endotoxin-stimulated THP-1 , a human monocytic cell line .

In this study , we report that both Exosurf and Survanta suppress <rna>TNF mRNA</rna> and secretion ( 85 +/- 4 % mean percent inhibition +/- SEM by Exosurf ; 71 +/- 6 % by Survanta ) by <cell_line>endotoxin-stimulated THP-1</cell_line> , a <cell_line>human monocytic cell line</cell_line> .


Because surfactant downregulated inflammatory cytokine production similarly in both normal human alveolar macrophages and the THP-1 cell line , we used this cell line to investigate whether surfactant affected transcriptional mechanisms .

Because surfactant downregulated <protein>inflammatory cytokine</protein> production similarly in both <cell_type>normal human alveolar macrophages</cell_type> and the <cell_line>THP-1 cell line</cell_line> , we used this <cell_line>cell line</cell_line> to investigate whether surfactant affected transcriptional mechanisms .


Specifically , we examined nuclear factor-kappa B ( NF-kappa B ) activation because it is crucial in transcriptional regulation of many inflammatory cytokine genes including TNF , IL-1 , and IL-6 .

Specifically , we examined <protein>nuclear factor-kappa B</protein> ( <protein>NF-kappa B</protein> ) activation because it is crucial in transcriptional regulation of many <dna>inflammatory cytokine genes</dna> including <dna>TNF</dna> , <dna>IL-1</dna> , and <dna>IL-6</dna> .


Electrophoretic mobility shift assays showed that both surfactants decreased activation of NF-kappa B .

Electrophoretic mobility shift assays showed that both surfactants decreased activation of <protein>NF-kappa B</protein> .


The presence of both p65 and p50 NF-kappa B components in LPS-activated THP-1 cells was confirmed by specific antibody induction of supershifts in mobility assays .

The presence of both <protein>p65</protein> and <protein>p50</protein> <protein>NF-kappa B components</protein> in LPS-activated <cell_line>THP-1 cells</cell_line> was confirmed by specific antibody induction of supershifts in mobility assays .


These results are the first to suggest that surfactant 's suppressive effects on inflammatory cytokine production may involve transcriptional regulation through inhibition of NF-kappa B activation .

These results are the first to suggest that surfactant 's suppressive effects on <protein>inflammatory cytokine</protein> production may involve transcriptional regulation through inhibition of <protein>NF-kappa B</protein> activation .


A cell type-specific enhancer in the human B7.1 gene regulated by NF-kappaB .

A <dna>cell type-specific enhancer</dna> in the <dna>human B7.1 gene</dna> regulated by <protein>NF-kappaB</protein> .


The costimulatory molecule B7.1 provides a second signal critical for T cell activation .

The <protein>costimulatory molecule B7.1</protein> provides a second signal critical for T cell activation .


The distribution of this integral membrane protein is restricted to certain tissues where its level of expression is modulated by multiple exogenous stimuli .

The distribution of this <protein>integral membrane protein</protein> is restricted to certain tissues where its level of expression is modulated by multiple exogenous stimuli .


To identify the molecular basis for specificity and inducibility , the chromatin configuration of the human B7.1 gene was examined in intact nuclei from various cell types .

To identify the molecular basis for specificity and inducibility , the <dna>chromatin</dna> configuration of the <dna>human B7.1 gene</dna> was examined in intact nuclei from various cell types .


The identification of a tissue-specific deoxyribonuclease I hypersensitive site approximately 3kb upstream of the transcription start site led to the characterization of a cell type-specific enhancer region .

The identification of a tissue-specific <dna>deoxyribonuclease I hypersensitive site</dna> approximately <dna>3kb upstream</dna> of the <dna>transcription start site</dna> led to the characterization of a <dna>cell type-specific enhancer region</dna> .


This 183-bp region was both cell type specific and responsive to two distinct stimuli , lipopolysaccharide and dibutyryl cAMP , known to regulate B7.1 expression .

This <dna>183-bp region</dna> was both cell type specific and responsive to two distinct stimuli , lipopolysaccharide and dibutyryl cAMP , known to regulate <protein>B7.1</protein> expression .


Deletional and site-directed mutagenesis revealed the presence of multiple functionally critical cis elements within this region , one of which was a nuclear factor ( NF ) -kappaB consensus sequence .

Deletional and site-directed mutagenesis revealed the presence of multiple functionally critical <dna>cis elements</dna> within this region , one of which was a <dna>nuclear factor ( NF ) -kappaB consensus sequence</dna> .


In B7.1-positive B cells , this element bound several members of the NF-kappaB family , transcription factors already implicated in signal transduction pathways relevant to B7.1 expression .

In <cell_type>B7.1-positive B cells</cell_type> , this element bound several members of the <protein>NF-kappaB family</protein> , <protein>transcription factors</protein> already implicated in signal transduction pathways relevant to <protein>B7.1</protein> expression .


This is the first description , to our knowledge , of regulatory elements that control expression of a gene encoding a B7 costimulatory molecule .

This is the first description , to our knowledge , of <dna>regulatory elements</dna> that control expression of a gene encoding a <protein>B7 costimulatory molecule</protein> .


Ubiquitinylation of transcription factors c-Jun and c-Fos using reconstituted ubiquitinylating enzymes .

Ubiquitinylation of <protein>transcription factors</protein> <protein>c-Jun</protein> and <protein>c-Fos</protein> using <protein>reconstituted ubiquitinylating enzymes</protein> .


Recombinant c-Jun and c-Fos were ubiquitinylated by the ubiquitin carrier enzymes E214K , E220K , or E232K in the presence of the ubiquitin-activating enzyme , E1 .

Recombinant <protein>c-Jun</protein> and <protein>c-Fos</protein> were ubiquitinylated by the <protein>ubiquitin carrier enzymes</protein> <protein>E214K</protein> , <protein>E220K</protein> , or <protein>E232K</protein> in the presence of the <protein>ubiquitin-activating enzyme</protein> , <protein>E1</protein> .


Addition of ubiquitin protein ligase E3 substantially enhanced the E214K -mediated ubiquitinylation of c-Jun and c-Fos .

Addition of <protein>ubiquitin protein ligase E3</protein> substantially enhanced the <protein>E214K</protein> -mediated ubiquitinylation of <protein>c-Jun</protein> and <protein>c-Fos</protein> .


Truncated c-Jun and c-Fos mutant proteins including wbJun and wbFos were also ubiquitinylated under the same conditions , suggesting the sites of ubiquitinylation are located within the dimerization and DNA binding domains of c-Jun and c-Fos .

<protein>Truncated c-Jun and c-Fos mutant proteins</protein> including <protein>wbJun</protein> and <protein>wbFos</protein> were also ubiquitinylated under the same conditions , suggesting the sites of ubiquitinylation are located within the <protein>dimerization and DNA binding domains</protein> of <protein>c-Jun</protein> and <protein>c-Fos</protein> .


The E3-dependent ubiquitinylation of c-Jun was inhibited upon the heterodimerization of c-Jun with c-Fos .

The E3-dependent ubiquitinylation of <protein>c-Jun</protein> was inhibited upon the heterodimerization of <protein>c-Jun</protein> with <protein>c-Fos</protein> .


Further addition of E220K significantly enhanced ubiquitinylation of c-Jun in the heterodimer suggesting a regulatory role of E220K .

Further addition of <protein>E220K</protein> significantly enhanced ubiquitinylation of <protein>c-Jun</protein> in the heterodimer suggesting a regulatory role of <protein>E220K</protein> .


Polyubiquitinylated c-Jun , wbFos , and wbJun , but not E220K-ubiquitinylated c-Jun , were readily degraded by the ATP-dependent 26 S multicatalytic proteases .

Polyubiquitinylated <protein>c-Jun</protein> , <protein>wbFos</protein> , and <protein>wbJun</protein> , but not <protein>E220K-ubiquitinylated c-Jun</protein> , were readily degraded by the <protein>ATP-dependent 26 S multicatalytic proteases</protein> .


These results suggest that the temporal control of c-Jun and c-Fos may be regulated through the ubiquitinylation pathways , and the ubiquitinylation of c-Jun and c-Fos may in turn be regulated in response to the heterodimerization between them and the cooperation between E220K and E3 mediated polyubiquitinylation .

These results suggest that the temporal control of <protein>c-Jun</protein> and <protein>c-Fos</protein> may be regulated through the ubiquitinylation pathways , and the ubiquitinylation of <protein>c-Jun</protein> and <protein>c-Fos</protein> may in turn be regulated in response to the heterodimerization between them and the cooperation between <protein>E220K</protein> and E3 mediated polyubiquitinylation .


Cloning and characterization of the murine B-cell specific transcriptional coactivator Bob1 .

Cloning and characterization of the <protein>murine B-cell specific transcriptional coactivator</protein> <protein>Bob1</protein> .


From a murine B-cell cDNA-library we have cloned a cDNA encoding the murine B-cell specific coactivator mBob1 .

From a <dna>murine B-cell cDNA-library</dna> we have cloned a <dna>cDNA</dna> encoding the <protein>murine B-cell specific coactivator</protein> <protein>mBob1</protein> .


The protein is the murine homologue to the recently described human coactivator Bob1 ( hBob1 ) , also referred to as OBF-1 or OCA-B .

The protein is the murine homologue to the recently described <protein>human coactivator Bob1</protein> ( <protein>hBob1</protein> ) , also referred to as <protein>OBF-1</protein> or <protein>OCA-B</protein> .


We have also characterized the genomic mBob1 clone .

We have also characterized the <protein>genomic mBob1 clone</protein> .


Analysis of its intron-exon structure has allowed identification of a C-terminal splice variant .

Analysis of its intron-exon structure has allowed identification of a <protein>C-terminal splice variant</protein> .


mBob1 is B-cell restricted , and is found in all B-cell lines representing different stages of B-cell differentiation .

<protein>mBob1</protein> is B-cell restricted , and is found in all <cell_line>B-cell lines</cell_line> representing different stages of B-cell differentiation .


mBob1 interacts with the octamer transcription factors Oct-1 and Oct-2 and stimulates transcription mediated by these factors .

<protein>mBob1</protein> interacts with the <protein>octamer transcription factors</protein> <protein>Oct-1</protein> and <protein>Oct-2</protein> and stimulates transcription mediated by these factors .


HIV glycoprotein 120 enhances intercellular adhesion molecule-1 gene expression in glial cells .

<protein>HIV glycoprotein 120</protein> enhances <protein>intercellular adhesion molecule-1</protein> gene expression in <cell_type>glial cells</cell_type> .


Involvement of Janus kinase /signal transducer and activator of transcription and protein kinase C signaling pathways .

Involvement of <protein>Janus kinase</protein> <protein>/signal transducer and activator of transcription</protein> and <protein>protein kinase C</protein> signaling pathways .


It is well established that the two major glial cells in the central nervous system ( CNS ) , astrocytes and microglia , are key participants in mediating the neurologic dysfunction associated with HIV infection of the CNS .

It is well established that the two major <cell_type>glial cells</cell_type> in the central nervous system ( CNS ) , <cell_type>astrocytes</cell_type> and <cell_type>microglia</cell_type> , are key participants in mediating the neurologic dysfunction associated with HIV infection of the CNS .


In this study , we investigated the ability of the major envelope glycoprotein of HIV , glycoprotein 120 ( gp120 ) , to regulate intercellular adhesion molecule-1 ( ICAM-1 ) expression in glial cells , because ICAM-1 is important in mediating immune responsiveness in the CNS , facilitating entry of HIV-infected cells into the CNS , and promoting syncytia formation .

In this study , we investigated the ability of the <protein>major envelope glycoprotein</protein> of HIV , <protein>glycoprotein 120</protein> ( <protein>gp120</protein> ) , to regulate <protein>intercellular adhesion molecule-1</protein> ( <protein>ICAM-1</protein> ) expression in <cell_type>glial cells</cell_type> , because <protein>ICAM-1</protein> is important in mediating immune responsiveness in the CNS , facilitating entry of <cell_type>HIV-infected cells</cell_type> into the CNS , and promoting syncytia formation .


Our results indicate that gp120 enhances ICAM-1 gene expression in primary rat astrocytes , primary human astrocytes , a human astroglioma cell line CRT , and primary rat microglia .

Our results indicate that <protein>gp120</protein> enhances <protein>ICAM-1</protein> gene expression in <cell_type>primary rat astrocytes</cell_type> , <cell_type>primary human astrocytes</cell_type> , a <cell_line>human astroglioma cell line CRT</cell_line> , and <cell_type>primary rat microglia</cell_type> .


The signal transduction events involved in gp120 -mediated enhancement of ICAM-1 appear to involve activation of both protein kinase C and tyrosine kinase , because inhibitors of protein kinase C and tyrosine kinase abrogate gp120 -mediated ICAM-1 expression in both astrocytes and microglia .

The signal transduction events involved in <protein>gp120</protein> -mediated enhancement of <protein>ICAM-1</protein> appear to involve activation of both <protein>protein kinase C</protein> and <protein>tyrosine kinase</protein> , because inhibitors of <protein>protein kinase C</protein> and <protein>tyrosine kinase</protein> abrogate <protein>gp120</protein> -mediated <protein>ICAM-1</protein> expression in both <cell_type>astrocytes</cell_type> and <cell_type>microglia</cell_type> .


Moreover , gp120 induces tyrosine phosphorylation of signal transducer and activator of transcription ( STAT-1 alpha ) as well as the Janus kinase ( JAK2 ) in glial cells .

Moreover , <protein>gp120</protein> induces tyrosine phosphorylation of <protein>signal transducer and activator of transcription</protein> ( <protein>STAT-1 alpha</protein> ) as well as the <protein>Janus kinase</protein> ( <protein>JAK2</protein> ) in <cell_type>glial cells</cell_type> .


We also demonstrate that gp120 -mediated ICAM-1 expression has functional significance , as it enhances the ability of monocytic cells to bind to gp120-stimulated human astrocytes in an ICAM-1 /beta 2 integrin -dependent fashion .

We also demonstrate that <protein>gp120</protein> -mediated <protein>ICAM-1</protein> expression has functional significance , as it enhances the ability of <cell_type>monocytic cells</cell_type> to bind to <cell_type>gp120-stimulated human astrocytes</cell_type> in an <protein>ICAM-1</protein> /beta 2 <protein>integrin</protein> -dependent fashion .


These results provide new insights into how gp120 can influence the involvement of glial cells in the pathogenesis of AIDS dementia complex .

These results provide new insights into how <protein>gp120</protein> can influence the involvement of <cell_type>glial cells</cell_type> in the pathogenesis of AIDS dementia complex .


IL-10 cooperates with TNF-alpha to activate HIV-1 from latently and acutely infected cells of monocyte/macrophage lineage .

<protein>IL-10</protein> cooperates with <protein>TNF-alpha</protein> to activate HIV-1 from <cell_type>latently and acutely infected cells</cell_type> of <cell_type>monocyte/macrophage lineage</cell_type> .


IL-10 is elevated in HIV-1-infected individuals and has been implicated in disease progression .

<protein>IL-10</protein> is elevated in HIV-1-infected individuals and has been implicated in disease progression .


In this study , we investigated the effects of IL-10 on the activation of HIV-1 from infected monocytes and macrophages .

In this study , we investigated the effects of <protein>IL-10</protein> on the activation of HIV-1 from <cell_type>infected monocytes</cell_type> and <cell_type>macrophages</cell_type> .


Although IL-10 alone did not induce HIV-1 replication , in the presence of TNF-alpha , IL-10 markedly enhanced virion production from a chronically infected promonocytic cell line ( U1 ) and in acutely infected monocyte-derived macrophages .

Although <protein>IL-10</protein> alone did not induce HIV-1 replication , in the presence of <protein>TNF-alpha</protein> , <protein>IL-10</protein> markedly enhanced virion production from a chronically infected <cell_line>promonocytic cell line</cell_line> ( <cell_line>U1</cell_line> ) and in acutely infected <cell_type>monocyte-derived macrophages</cell_type> .


Neutralizing mAbs to IL-10 and TNF-alpha indicated that both cytokines were essential for the induction and were required to generate a synergistic increase in virus expression .

Neutralizing <protein>mAbs</protein> to <protein>IL-10</protein> and <protein>TNF-alpha</protein> indicated that both <protein>cytokines</protein> were essential for the induction and were required to generate a synergistic increase in virus expression .


The effects of the two cytokines were distinguishable functionally since pretreatment with TNF-alpha attenuated the cytokine cooperativity , while pretreatment with IL-10 potentiated their cooperativity , suggesting that IL-10 and TNF-alpha play different roles in the activation of virus .

The effects of the two <protein>cytokines</protein> were distinguishable functionally since pretreatment with <protein>TNF-alpha</protein> attenuated the <protein>cytokine</protein> cooperativity , while pretreatment with <protein>IL-10</protein> potentiated their cooperativity , suggesting that <protein>IL-10</protein> and <protein>TNF-alpha</protein> play different roles in the activation of virus .


Northern blot analysis as well as Ab blocking and cytokine secretion studies indicated that the induction of either endogenous TNF-alpha or IL-10 was not involved in the cooperativity , nor was an up-regulation of TNF-alpha receptors .

Northern blot analysis as well as Ab blocking and <protein>cytokine</protein> secretion studies indicated that the induction of either <protein>endogenous TNF-alpha</protein> or <protein>IL-10</protein> was not involved in the cooperativity , nor was an up-regulation of <protein>TNF-alpha receptors</protein> .


In combination with TNF-alpha , IL-10 stimulated activating protein-1 ( AP-1 ) and nuclear factor ( NF ) -kappa B binding activities and cooperated to increase HIV-1 steady-state mRNA levels and enhance long terminal repeat -directed transcription through activation of the NF-kappa B binding sites , suggesting the IL-10 effect occurs at least in part at the transcriptional level .

In combination with <protein>TNF-alpha</protein> , <protein>IL-10</protein> stimulated <protein>activating protein-1</protein> ( <protein>AP-1</protein> ) and <protein>nuclear factor ( NF ) -kappa B</protein> binding activities and cooperated to increase HIV-1 steady-state mRNA levels and enhance <dna>long terminal repeat</dna> -directed transcription through activation of the <dna>NF-kappa B binding sites</dna> , suggesting the <protein>IL-10</protein> effect occurs at least in part at the transcriptional level .


These results indicate that IL-10 , in addition to down-regulating the cellular immune response to HIV-1 , may also play a role in TNF-alpha -mediated activation of HIV-1 replication in the monocyte/macrophage lineage .

These results indicate that <protein>IL-10</protein> , in addition to down-regulating the cellular immune response to HIV-1 , may also play a role in <protein>TNF-alpha</protein> -mediated activation of HIV-1 replication in the <cell_type>monocyte/macrophage lineage</cell_type> .


Interaction of HTLV-I Tax with the human proteasome : implications for NF-kappa B induction .

Interaction of <protein>HTLV-I Tax</protein> with the <protein>human proteasome</protein> : implications for <protein>NF-kappa B</protein> induction .


The human T-cell leukemia virus type I ( HTLV-I ) has been etiologically associated with the development of the adult T-cell leukemia ( ATL ) as well as degenerative neurologic syndrome termed tropical spastic paraparesis ( TSP ) .


HTLV-I encodes a potent transactivator protein termed Tax that appears to play an important role in the process of T-cell immortalization .

HTLV-I encodes a potent <protein>transactivator</protein> protein termed <protein>Tax</protein> that appears to play an important role in the process of T-cell immortalization .


Even though the mechanisms by which Tax induces transformation are still unknown , it seems likely that the ability of Tax to alter the expression of many cellular genes plays an important part in this process .

Even though the mechanisms by which <protein>Tax</protein> induces transformation are still unknown , it seems likely that the ability of <protein>Tax</protein> to alter the expression of many <dna>cellular genes</dna> plays an important part in this process .


Tax does not bind directly to DNA but rather deregulates the activity of cellular transcription factors .

<protein>Tax</protein> does not bind directly to DNA but rather deregulates the activity of <protein>cellular transcription factors</protein> .


One family of host transcription factors whose activity is altered by Tax includes NF-kappa B/Rel .

One family of <protein>host transcription factors</protein> whose activity is altered by <protein>Tax</protein> includes <protein>NF-kappa B/Rel</protein> .


These transcription factors are post-transcriptionally regulated by their assembly with a second family of inhibitory proteins termed I kappa B that serve to sequester the NF-kappa B/Rel complexes in the cytoplasm .

These <protein>transcription factors</protein> are post-transcriptionally regulated by their assembly with a second family of <protein>inhibitory proteins</protein> termed <protein>I kappa B</protein> that serve to sequester the <protein>NF-kappa B/Rel complexes</protein> in the cytoplasm .


Upon cellular activation , I kappa B alpha is phosphorylated , polyubiquitinated , and degraded in the proteasome .

Upon cellular activation , <protein>I kappa B alpha</protein> is phosphorylated , polyubiquitinated , and degraded in the <protein>proteasome</protein> .


This proteolytic event liberates NF-kappa B , permitting its rapid translocation into the nucleus where it binds to its cognate enhancer elements .

This proteolytic event liberates <protein>NF-kappa B</protein> , permitting its rapid translocation into the nucleus where it binds to its <dna>cognate enhancer elements</dna> .


Similarly , the p105 precursor of the NF-kappa B p50 subunit is also post-translationally processed in the proteasome .

Similarly , the <protein>p105 precursor</protein> of the <protein>NF-kappa B</protein> <protein>p50 subunit</protein> is also post-translationally processed in the <protein>proteasome</protein> .


The mechanisms by which Tax activates NF-kappa B remain unclear , and findings presented in the literature are often controversial .

The mechanisms by which <protein>Tax</protein> activates <protein>NF-kappa B</protein> remain unclear , and findings presented in the literature are often controversial .


We identified a physical interaction between Tax and the HsN3 subunit of the human proteasome .

We identified a physical interaction between <protein>Tax</protein> and the <protein>HsN3 subunit</protein> of the <protein>human proteasome</protein> .


This raises the intriguing possibility that physical association of the HsN3 proteasome subunit with HTLV-I Tax coupled with the independent interaction of Tax with either p100 or p65- I kappa B alpha targets these cytoplasmic NF-kappa B/Rel complexes to the proteasome for processing .

This raises the intriguing possibility that physical association of the <protein>HsN3 proteasome subunit</protein> with <protein>HTLV-I Tax</protein> coupled with the independent interaction of <protein>Tax</protein> with either p100 or p65- <protein>I kappa B alpha</protein> targets these <protein>cytoplasmic NF-kappa B/Rel complexes</protein> to the <protein>proteasome</protein> for processing .


Immunophenotype of intraductal carcinoma .


OBJECTIVE -- Mammography and breast-conserving therapy have focused attention on the classification of intraductal carcinoma ( IDC ) and emphasized the prognostic importance of comedo versus noncomedo variants .


We used histochemical markers to define the immunophenotype of 43 IDCs with respect to comedo versus noncomedo status and patterns of angiogenesis .


RESULTS -- Reactions in comedo carcinomas were significantly negative for estrogen receptor and progesterone receptor , and positive for p53 and HER-2/neu more often than the noncomedo variant .

RESULTS -- Reactions in comedo carcinomas were significantly negative for <protein>estrogen receptor</protein> and <protein>progesterone receptor</protein> , and positive for <protein>p53</protein> and <protein>HER-2/neu</protein> more often than the noncomedo variant .


All seven IDCs associated with Paget 's disease showed positive reactions for HER-2/neu .

All seven IDCs associated with Paget 's disease showed positive reactions for <protein>HER-2/neu</protein> .


Basement membrane immunoreactivity for type IV collagen and laminin was discontinuous in most examples of IDC regardless of type , with a trend toward more intense staining in comedo than in noncomedo carcinomas .

Basement membrane immunoreactivity for <protein>type IV collagen</protein> and <protein>laminin</protein> was discontinuous in most examples of IDC regardless of type , with a trend toward more intense staining in comedo than in noncomedo carcinomas .


Periductal angiogenesis was not significantly related to the type of IDC but was more pronounced with comedo carcinomas .


CONCLUSIONS -- These observations indicate that there are immunophenotypic correlates to the current structural classification of IDC .


The immunophenotype of IDC is helpful in subclassifying an IDC and could prove useful as a prognostic indicator for local control in patients treated by breast-conserving therapy .


Inhibition of protein phosphatase 2A induces serine/threonine phosphorylation , subcellular redistribution , and functional inhibition of STAT3 .

Inhibition of <protein>protein phosphatase 2A</protein> induces serine/threonine phosphorylation , subcellular redistribution , and functional inhibition of <protein>STAT3</protein> .


Signal transducers and activators of transcription ( STATs ) are rapidly phosphorylated on tyrosine residues in response to cytokine and growth factor stimulation of cell surface receptors .

<protein>Signal transducers and activators of transcription</protein> ( <protein>STATs</protein> ) are rapidly phosphorylated on tyrosine residues in response to <protein>cytokine</protein> and <protein>growth factor</protein> stimulation of <protein>cell surface receptors</protein> .


STATs hereafter are translocated to the nucleus where they act as transcription factors .

<protein>STATs</protein> hereafter are translocated to the nucleus where they act as <protein>transcription factors</protein> .


Recent reports suggest that serine phosphorylation of STATs also is involved in the regulation of STAT -mediated gene transcription .

Recent reports suggest that serine phosphorylation of <protein>STATs</protein> also is involved in the regulation of <protein>STAT</protein> -mediated gene transcription .


Here , we studied the role of serine/threonine phosphatases in STAT3 signaling in human antigen-specific CD4 ( + ) T cell lines and cutaneous T cell lymphoma lines , expressing a constitutively activated STAT3 .

Here , we studied the role of <protein>serine/threonine phosphatases</protein> in <protein>STAT3</protein> signaling in <cell_line>human antigen-specific CD4 ( + ) T cell lines</cell_line> and <cell_line>cutaneous T cell lymphoma lines</cell_line> , expressing a constitutively activated <protein>STAT3</protein> .


We show that an inhibitor of protein phosphatases ( PPs ) PP1/PP2A , calyculin A , induces ( i ) phosphorylation of STAT3 on serine and threonine residues , ( ii ) inhibition of STAT3 tyrosine phosphorylation and DNA binding activity , and ( iii ) relocation of STAT3 from the nucleus to the cytoplasm .

We show that an inhibitor of <protein>protein phosphatases</protein> ( <protein>PPs</protein> ) <protein>PP1/PP2A</protein> , <protein>calyculin A</protein> , induces ( i ) phosphorylation of <protein>STAT3</protein> on serine and threonine residues , ( ii ) inhibition of <protein>STAT3</protein> tyrosine phosphorylation and DNA binding activity , and ( iii ) relocation of <protein>STAT3</protein> from the nucleus to the cytoplasm .


Similar results were obtained with other PP2A inhibitors ( okadaic acid , endothall thioanhydride ) but not with inhibitors of PP1 ( tautomycin ) or PP2B ( cyclosporine A ) .

Similar results were obtained with other PP2A inhibitors ( okadaic acid , endothall thioanhydride ) but not with inhibitors of <protein>PP1</protein> ( tautomycin ) or <protein>PP2B</protein> ( cyclosporine A ) .


Pretreatment with the broad serine/threonine kinase inhibitor staurosporine partly blocked the calyculin A -induced STAT3 phosphorylation , whereas inhibitors of serine/threonine kinases , such as mitogen-activated protein kinase-1 extracellular-regulated kinase-kinase , mitogen-activated protein p38 kinase , and phosphatidylinositol 3-kinase , did not .

Pretreatment with the broad serine/threonine kinase inhibitor staurosporine partly blocked the <protein>calyculin A</protein> -induced <protein>STAT3</protein> phosphorylation , whereas inhibitors of <protein>serine/threonine kinases</protein> , such as <protein>mitogen-activated protein kinase-1 extracellular-regulated kinase-kinase</protein> , <protein>mitogen-activated protein p38 kinase</protein> , and <protein>phosphatidylinositol 3-kinase</protein> , did not .


In conclusion , we provide evidence that PP2A plays a crucial role in the regulation of STAT3 phosphorylation and subcellular distribution in T cells .

In conclusion , we provide evidence that <protein>PP2A</protein> plays a crucial role in the regulation of <protein>STAT3</protein> phosphorylation and subcellular distribution in <cell_type>T cells</cell_type> .


Moreover , our findings suggest that the level of STAT3 phosphorylation is balanced between a staurosporine-sensitive kinase ( s ) and PP2A .

Moreover , our findings suggest that the level of <protein>STAT3</protein> phosphorylation is balanced between a <protein>staurosporine-sensitive kinase</protein> ( s ) and <protein>PP2A</protein> .


Polyamines in human breast cancer and its relations to classical prognostic features : clinical implications .


Experimental evidence suggest an important role of polyamines in breast cancer development .


Polyamines have been determined in tissue and erythrocyte samples from 100 patients with primary invasive breast cancer and 30 patients with fibroadenomas .


Statistical analysis was performed in order to determine the prognostic value of the polyamine patterns of tumor tissues and erythrocytes in comparison with clinical and histological prognostic factors .


In malignant tissues , polyamine levels were significantly higher than in benign tissues .


They correlated with markers of tumor aggressivity ( axillary node involvement and especially with markers of high mitotic rate as Ki-67 staining , histological grade ) .


No correlation was found between estrogen and progesterone status , tumor size and polyamine concentrations .


Erythrocyte polyamines levels were identical between cancer patients and controls .


The knowledge of the polyamine pattern in breast cancer could become useful in clinical practice particularly if polyamine metabolism is targeted as a therapeutic approach .


Signal transduction pathways triggered by the FcepsilonRIIb receptor ( CD23 ) in human monocytes lead to nuclear factor-kappaB activation .

Signal transduction pathways triggered by the <protein>FcepsilonRIIb receptor</protein> ( <protein>CD23</protein> ) in <cell_type>human monocytes</cell_type> lead to <protein>nuclear factor-kappaB</protein> activation .


BACKGROUND : Alveolar macrophages play a key role in the initiation of the inflammatory reaction of allergic asthma .

BACKGROUND : <cell_type>Alveolar macrophages</cell_type> play a key role in the initiation of the inflammatory reaction of allergic asthma .


Alveolar macrophages and peripheral blood monocytes are activated when IgE/allergen immune complexes bind to the CD23 receptor , which leads to the production of inflammatory cytokines .

<cell_type>Alveolar macrophages</cell_type> and <cell_type>peripheral blood monocytes</cell_type> are activated when <protein>IgE/allergen immune complexes</protein> bind to the <protein>CD23 receptor</protein> , which leads to the production of <protein>inflammatory cytokines</protein> .


OBJECTIVE : We sought to investigate the molecular mechanisms regulating this early inflammatory response .


We have focused on the study of the signal transduction pathways triggered by CD23 in human monocytes and the promonocytic cell line U937 .

We have focused on the study of the signal transduction pathways triggered by <protein>CD23</protein> in <cell_type>human monocytes</cell_type> and the <cell_line>promonocytic cell line U937</cell_line> .


METHODS : CD23 was cross-linked in human monocytes and U937 cells with IgE immune complexes .

METHODS : <protein>CD23</protein> was cross-linked in <cell_type>human monocytes</cell_type> and <cell_line>U937 cells</cell_line> with <protein>IgE immune complexes</protein> .


Surface expression of CD23 was determined by FACS analysis .

Surface expression of <protein>CD23</protein> was determined by FACS analysis .


Transcription factor activation and gene transcription were studied by gel-shift assays and Northern blot analysis , respectively .

<protein>Transcription factor</protein> activation and gene transcription were studied by gel-shift assays and Northern blot analysis , respectively .


IkappaBalpha phosphorylation and degradation was analyzed by Western blot .

<protein>IkappaBalpha</protein> phosphorylation and degradation was analyzed by Western blot .


RESULTS : Nuclear factor ( NF ) -kappaB is the main transcription factor involved in the gene activation that follows CD23 cross-linking in monocytes .

RESULTS : <protein>Nuclear factor ( NF ) -kappaB</protein> is the main transcription factor involved in the gene activation that follows <protein>CD23</protein> cross-linking in <cell_type>monocytes</cell_type> .


CD23-induced NF-kappaB is a heterodimer composed of p65/p50 subunits .

<protein>CD23-induced NF-kappaB</protein> is a heterodimer composed of <protein>p65/p50 subunits</protein> .


NF-kappaB nuclear translocation is secondary to the phosphorylation and subsequent degradation of the NF-kappaB inhibitory molecule IkappaBalpha .

NF-kappaB nuclear translocation is secondary to the phosphorylation and subsequent degradation of the <protein>NF-kappaB inhibitory molecule</protein> <protein>IkappaBalpha</protein> .


Tyrosine kinase -dependent , and not protein kinase C -dependent , pathways mediate CD23 -triggered NF-kappaB activation but do not participate in the direct phosphorylation of IkappaBalpha .

<protein>Tyrosine kinase</protein> -dependent , and not <protein>protein kinase C</protein> -dependent , pathways mediate <protein>CD23</protein> -triggered <protein>NF-kappaB</protein> activation but do not participate in the direct phosphorylation of <protein>IkappaBalpha</protein> .


IkappaBalpha degradation and NF-kappaB nuclear translocation correlate with transcriptional activation of the inflammatory cytokines TNF-alpha and IL-1beta .

<protein>IkappaBalpha</protein> degradation and <protein>NF-kappaB</protein> nuclear translocation correlate with transcriptional activation of the <protein>inflammatory cytokines</protein> <protein>TNF-alpha</protein> and IL-1beta .


CONCLUSIONS : NF-kappaB is the main transcription factor involved in the signal transduction pathway of CD23 in monocytes .

CONCLUSIONS : <protein>NF-kappaB</protein> is the main transcription factor involved in the signal transduction pathway of <protein>CD23</protein> in <cell_type>monocytes</cell_type> .


Suppression of TNFalpha -mediated NFkappaB activity by myricetin and other flavonoids through downregulating the activity of IKK in ECV304 cells .

Suppression of <protein>TNFalpha</protein> -mediated <protein>NFkappaB</protein> activity by myricetin and other flavonoids through downregulating the activity of <protein>IKK</protein> in <cell_line>ECV304 cells</cell_line> .


Flavonoids are a group of naturally-occurring phenolic compounds in the plant kingdom , and many flavonoids are found with vascular protective properties .


Nevertheless how the protective response is exerted by flavonoids is not well characterized .


In view of the nuclear factor-kappaB ( NFkappaB ) may play a central role in the initiation of atherosclerosis , prevention of the activation of NFkappaB represents an important role in protecting vascular injury .

In view of the <protein>nuclear factor-kappaB</protein> ( <protein>NFkappaB</protein> ) may play a central role in the initiation of atherosclerosis , prevention of the activation of <protein>NFkappaB</protein> represents an important role in protecting vascular injury .


In this study , the effects of flavonoids on NFkappaB /inhibitor-kappaB ( IkappaB ) system in ECV304 cells activated with tumor necrosis factor-alpha ( TNFalpha ) were examined .

In this study , the effects of flavonoids on <protein>NFkappaB</protein> /inhibitor-kappaB ( <protein>IkappaB</protein> ) system in <cell_line>ECV304 cells</cell_line> activated with <protein>tumor necrosis factor-alpha</protein> ( <protein>TNFalpha</protein> ) were examined .


We investigated the inhibitory action of six flavonoids on IkappaB kinase ( IKK ) activity , an enzyme recently found to phosphorylate critical serine residues of IkappaB for degradation .

We investigated the inhibitory action of six flavonoids on <protein>IkappaB kinase</protein> ( <protein>IKK</protein> ) activity , an enzyme recently found to phosphorylate critical serine residues of IkappaB for degradation .


Of six flavonoids tested , myricetin was found to strongly inhibit IKK kinase activity , and prevent the degradation of IkappaBalpha and IkappaBbeta in activated endothelial cells .

Of six flavonoids tested , myricetin was found to strongly inhibit <protein>IKK</protein> kinase activity , and prevent the degradation of <protein>IkappaBalpha</protein> and <protein>IkappaBbeta</protein> in activated endothelial cells .


Furthermore , myricetin was also found to inhibit NFkappaB activity correlated with suppression of monocyte adhesion to ECV304 cells .

Furthermore , myricetin was also found to inhibit <protein>NFkappaB</protein> activity correlated with suppression of monocyte adhesion to <cell_line>ECV304 cells</cell_line> .


Therefore we conclude that flavonoids may be of therapeutic value for vascular disease through down regulation of NFkappaB /IkappaB system .

Therefore we conclude that flavonoids may be of therapeutic value for vascular disease through down regulation of <protein>NFkappaB</protein> <protein>/IkappaB</protein> system .


Copyright 1999 Wiley-Liss , Inc .


Bcl-2 -mediated drug resistance : inhibition of apoptosis by blocking nuclear factor of activated T lymphocytes ( NFAT ) -induced Fas ligand transcription .

<protein>Bcl-2</protein> -mediated drug resistance : inhibition of apoptosis by blocking <protein>nuclear factor of activated T lymphocytes</protein> ( <protein>NFAT</protein> ) -induced <protein>Fas</protein> ligand transcription .


Bcl-2 inhibits apoptosis induced by a variety of stimuli , including chemotherapy drugs and glucocorticoids .

<protein>Bcl-2</protein> inhibits apoptosis induced by a variety of stimuli , including chemotherapy drugs and glucocorticoids .


It is generally accepted that Bcl-2 exerts its antiapoptotic effects mainly by dimerizing with proapoptotic members of the Bcl-2 family such as Bax and Bad .

It is generally accepted that <protein>Bcl-2</protein> exerts its antiapoptotic effects mainly by dimerizing with proapoptotic members of the <protein>Bcl-2 family</protein> such as <protein>Bax</protein> and <protein>Bad</protein> .


However , the mechanism of the antiapoptotic effects is unclear .


Paclitaxel and other drugs that disturb microtubule dynamics kill cells in a Fas /Fas ligand ( FasL ) -dependent manner ; antibody to FasL inhibits paclitaxel-induced apoptosis .

Paclitaxel and other drugs that disturb <protein>microtubule</protein> dynamics kill cells in a <protein>Fas</protein> <protein>/Fas ligand</protein> ( <protein>FasL</protein> ) -dependent manner ; antibody to <protein>FasL</protein> inhibits paclitaxel-induced apoptosis .


We have found that Bcl-2 overexpression leads to the prevention of chemotherapy ( paclitaxel ) -induced expression of FasL and blocks paclitaxel-induced apoptosis .

We have found that <protein>Bcl-2</protein> overexpression leads to the prevention of chemotherapy ( paclitaxel ) -induced expression of <protein>FasL</protein> and blocks paclitaxel-induced apoptosis .


The mechanism of this effect is that Bcl-2 prevents the nuclear translocation of NFAT ( nuclear factor of activated T lymphocytes , a transcription factor activated by microtubule damage ) by binding and sequestering calcineurin , a calcium-dependent phosphatase that must dephosphorylate NFAT to move to the nucleus .

The mechanism of this effect is that <protein>Bcl-2</protein> prevents the nuclear translocation of <protein>NFAT</protein> ( <protein>nuclear factor of activated T lymphocytes</protein> , a <protein>transcription factor</protein> activated by <protein>microtubule</protein> damage ) by binding and sequestering calcineurin , a calcium-dependent phosphatase that must dephosphorylate <protein>NFAT</protein> to move to the nucleus .


Without NFAT nuclear translocation , the FasL gene is not transcribed .

Without <protein>NFAT</protein> nuclear translocation , the <protein>FasL</protein> gene is not transcribed .


Thus , it appears that paclitaxel and other drugs that disturb microtubule function kill cells at least in part through the induction of FasL .

Thus , it appears that paclitaxel and other drugs that disturb <protein>microtubule</protein> function kill cells at least in part through the induction of <protein>FasL</protein> .


Furthermore , Bcl-2 antagonizes drug-induced apoptosis by inhibiting calcineurin activation , blocking NFAT nuclear translocation , and preventing FasL expression .

Furthermore , <protein>Bcl-2</protein> antagonizes drug-induced apoptosis by inhibiting <protein>calcineurin</protein> activation , blocking <protein>NFAT</protein> nuclear translocation , and preventing <protein>FasL</protein> expression .


The effects of Bcl-2 can be overcome , at least partially , through phosphorylation of Bcl-2 .

The effects of <protein>Bcl-2</protein> can be overcome , at least partially , through phosphorylation of <protein>Bcl-2</protein> .


Phosphorylated Bcl-2 can not bind calcineurin , and NFAT activation , FasL expression , and apoptosis can occur after Bcl-2 phosphorylation .

Phosphorylated <protein>Bcl-2</protein> can not bind <protein>calcineurin</protein> , and <protein>NFAT</protein> activation , <protein>FasL</protein> expression , and apoptosis can occur after <protein>Bcl-2</protein> phosphorylation .


MHC-peptide ligand interactions establish a functional threshold for antigen-specific T cell recognition .


Antigen-specific T cell recognition is dependent on the functional density of the TCR -ligand , which consists of specific MHC molecules and a specifically bound peptide .

Antigen-specific T cell recognition is dependent on the functional density of the <protein>TCR</protein> -ligand , which consists of specific <protein>MHC molecules</protein> and a specifically bound peptide .


We have examined the influence of the affinity and concentration of exogenous peptide and the density of specific MHC molecules on the proliferation of a CD4+ , DQA1*0501/DQB1*0201 ( DQ2.1 ) -restricted , HSV-2-specific T cell clone .

We have examined the influence of the affinity and concentration of exogenous peptide and the density of specific <protein>MHC molecules</protein> on the proliferation of a <cell_line>CD4+ , DQA1*0501/DQB1*0201 ( DQ2.1 ) -restricted , HSV-2-specific T cell clone</cell_line> .


Using antigen peptide analogs with different mutations of known DQ2-anchor residues , T cell response was reduced in an peptide-affinity and - concentration specific manner .


The decrease using weaker binding peptides was gradual as stimulation with a peptide with intermediate affinity yielded intermediate T cell proliferation and the poorest binding peptide induced an even weaker T cell response .

The decrease using weaker binding peptides was gradual as stimulation with a peptide with intermediate affinity yielded intermediate <cell_type>T cell</cell_type> proliferation and the poorest binding peptide induced an even weaker <cell_type>T cell</cell_type> response .


MHC class II density on the APC was modified using DQ2 homo -and heterozygous B-LCLs as APCs , however this variation of MHC concentration had no effect on T cell proliferation .

<protein>MHC class II</protein> density on the <cell_type>APC</cell_type> was modified using <cell_line>DQ2 homo -and heterozygous B-LCLs</cell_line> as <cell_type>APCs</cell_type> , however this variation of MHC concentration had no effect on <cell_type>T cell</cell_type> proliferation .


We interpret this as a reflection of a low threshold for activation of the T cell clone , in which peptide- MHC avidity is the over-riding determinant of the strength of ligand signal .

We interpret this as a reflection of a low threshold for activation of the <cell_line>T cell clone</cell_line> , in which peptide- <protein>MHC</protein> avidity is the over-riding determinant of the strength of ligand signal .


Regulatory effects of interleukin-11 during acute lung inflammatory injury .

Regulatory effects of <protein>interleukin-11</protein> during acute lung inflammatory injury .


The role of interleukin-11 ( IL-11 ) was evaluated in the IgG immune complex model of acute lung injury in rats .

The role of <protein>interleukin-11</protein> ( <protein>IL-11</protein> ) was evaluated in the <protein>IgG immune complex</protein> model of acute lung injury in rats .


IL-11 mRNA and protein were both up-regulated during the course of this inflammatory response .

<rna>IL-11 mRNA</rna> and protein were both up-regulated during the course of this inflammatory response .


Exogenously administered IL-11 substantially reduced , in a dose-dependent manner , the intrapulmonary accumulation of neutrophils and the lung vascular leak of albumin .

Exogenously administered <protein>IL-11</protein> substantially reduced , in a dose-dependent manner , the intrapulmonary accumulation of <cell_type>neutrophils</cell_type> and the lung vascular leak of <protein>albumin</protein> .


These in vivo anti-inflammatory effects of IL-11 were associated with reduced NF-kappaB activation in lung , reduced levels of tumor necrosis factor alpha ( TNF-alpha ) in bronchoalveolar lavage ( BAL ) fluids , and diminished up-regulation of lung vascular ICAM-1 .

These in vivo anti-inflammatory effects of <protein>IL-11</protein> were associated with reduced <protein>NF-kappaB</protein> activation in lung , reduced levels of <protein>tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) in bronchoalveolar lavage ( BAL ) fluids , and diminished up-regulation of <protein>lung vascular ICAM-1</protein> .


It is interesting that IL-11 did not affect BAL fluid content of the CXC chemokines , macrophage inflammatory protein-2 ( MIP-2 ) and cytokine-inducible neutrophil chemoattractant ( CINC ) ; the presence of IL-11 did not affect these chemokines .

It is interesting that <protein>IL-11</protein> did not affect BAL fluid content of the <protein>CXC chemokines</protein> , <protein>macrophage inflammatory protein-2</protein> ( <protein>MIP-2</protein> ) and <protein>cytokine-inducible neutrophil chemoattractant</protein> ( <protein>CINC</protein> ) ; the presence of <protein>IL-11</protein> did not affect these <protein>chemokines</protein> .


However , BAL content of C5a was reduced by IL-11 .

However , BAL content of C5a was reduced by <protein>IL-11</protein> .


These data indicate that IL-11 is a regulatory cytokine in the lung and that , like other members of this family , its anti-inflammatory properties appear to be linked to its suppression of NF-kappaB activation , diminished production of TNF-alpha , and reduced up-regulation of lung vascular ICAM-1 .

These data indicate that <protein>IL-11</protein> is a <protein>regulatory cytokine</protein> in the lung and that , like other members of this family , its anti-inflammatory properties appear to be linked to its suppression of <protein>NF-kappaB</protein> activation , diminished production of <protein>TNF-alpha</protein> , and reduced up-regulation of <protein>lung vascular ICAM-1</protein> .


Thrombopoietin induces tyrosine phosphorylation of Stat3 and Stat5 in human blood platelets .

<protein>Thrombopoietin</protein> induces tyrosine phosphorylation of <protein>Stat3</protein> and <protein>Stat5</protein> in <cell_type>human blood platelets</cell_type> .


Thrombopoietin is known to be essential for megakaryocytopoiesis and thrombopoiesis .

<protein>Thrombopoietin</protein> is known to be essential for megakaryocytopoiesis and thrombopoiesis .


Recently , we and others have shown that thrombopoietin induces rapid tyrosine phosphorylation of Jak2 and other proteins in human platelets and BaF3 cells , genetically engineered to express c-Mpl , a receptor for thrombopoietin .

Recently , we and others have shown that <protein>thrombopoietin</protein> induces rapid tyrosine phosphorylation of <protein>Jak2</protein> and other proteins in <cell_type>human platelets</cell_type> and <cell_line>BaF3 cells</cell_line> , genetically engineered to express <protein>c-Mpl</protein> , a receptor for <protein>thrombopoietin</protein> .


The Jak family of tyrosine kinases are known to mediate some of the effects of cytokines or hematopoietic growth factors by recruitment and tyrosine phosphorylation of a variety of Stat ( signal transducers and activators of transcription ) proteins .

The Jak family of <protein>tyrosine kinases</protein> are known to mediate some of the effects of <protein>cytokines</protein> or <protein>hematopoietic growth factors</protein> by recruitment and tyrosine phosphorylation of a variety of <protein>Stat</protein> ( <protein>signal transducers and activators of transcription</protein> ) proteins .


Hence , we have investigated whether Stat proteins are present in platelets and , if so , whether they become tyrosine phosphorylated in response to thrombopoietin .

Hence , we have investigated whether <protein>Stat proteins</protein> are present in <cell_type>platelets</cell_type> and , if so , whether they become tyrosine phosphorylated in response to <protein>thrombopoietin</protein> .


We immunologically identified Stat1 , Stat2 , Stat3 , and Stat5 in human platelet lysates .

We immunologically identified <protein>Stat1</protein> , <protein>Stat2</protein> , <protein>Stat3</protein> , and <protein>Stat5</protein> in human platelet lysates .


Thrombopoietin induced tyrosine phosphorylation of Stat3 and Stat5 in these cells .

<protein>Thrombopoietin</protein> induced tyrosine phosphorylation of <protein>Stat3</protein> and <protein>Stat5</protein> in these cells .


Thrombopoietin also induced tyrosine phosphorylation of Stat3 and Stat5 in FDCP-2 cells genetically engineered to constitutively express human c-Mpl .

<protein>Thrombopoietin</protein> also induced tyrosine phosphorylation of <protein>Stat3</protein> and <protein>Stat5</protein> in <cell_line>FDCP-2 cells</cell_line> genetically engineered to constitutively express <protein>human c-Mpl</protein> .


Thus , our data indicate that Stat3 and Stat5 may be involved in signal transduction after ligand binding to c-Mpl and that this event may have a role in megakaryopoiesis/thrombopoiesis or possibly a mature platelet function such as aggregation .

Thus , our data indicate that <protein>Stat3</protein> and <protein>Stat5</protein> may be involved in signal transduction after ligand binding to <protein>c-Mpl</protein> and that this event may have a role in megakaryopoiesis/thrombopoiesis or possibly a mature platelet function such as aggregation .


Mechanisms that contribute to the development of lymphoid malignancies : roles for genetic alterations and cytokine production .

Mechanisms that contribute to the development of lymphoid malignancies : roles for genetic alterations and <protein>cytokine</protein> production .


Recent studies have defined genetic alterations commonly associated with transformed lymphocytes .

Recent studies have defined genetic alterations commonly associated with <cell_line>transformed lymphocytes</cell_line> .


This review suggests roles for these alterations in the development of lymphoid neoplasms .


Damage to the genes encoding proteins that function in intracellular signaling , transcription , or regulation of the cell cycle has been identified and linked at varying degrees to the progression of certain lymphoid malignancies .


An understanding of the mechanistic consequences following such genetic alterations is essential to an understanding of the development of these lymphoid neoplasms .


In contrast , it is also becoming clear that the dysregulated expression of proteins that are not genetically altered can also contribute to the progression of lymphoid malignancies .


One such example is the excessive expression of `` normal '' lymphokines of cytokines which accompanies many lymphoproliferative diseases .

One such example is the excessive expression of <protein>`` normal '' lymphokines</protein> of <protein>cytokines</protein> which accompanies many lymphoproliferative diseases .


The dysregulated expression of cytokines during malignancy can result in the augmentation of growth of transformed lymphocytes , as well as an alteration of the anti-tumor immune response .

The dysregulated expression of <protein>cytokines</protein> during malignancy can result in the augmentation of growth of <cell_line>transformed lymphocytes</cell_line> , as well as an alteration of the anti-tumor immune response .


The latter mechanism is especially important because evasion of the impending immune response is a prerequisite for the progression of lymphoproliferative diseases .


Taken together , this review supports the notion that the development of lymphoid malignancies is multifactorial , involving genetic alterations as well as dysregulated cytokine expression .

Taken together , this review supports the notion that the development of lymphoid malignancies is multifactorial , involving genetic alterations as well as dysregulated <protein>cytokine</protein> expression .


Dehydroepiandrosterone modulation of lipopolysaccharide-stimulated monocyte cytotoxicity .


Dehydroepiandrosterone ( DHEA ) , the predominant androgen secreted by the adrenal cortex , can be converted to both potent androgens and estrogens .


In addition to its role as a precursor for other steroid hormones , DHEA has been proposed to play an important role in immunity .


This study has investigated DHEA modulation of LPS-induced monocyte cytotoxicity .


Cytotoxicity markers assessed include tumor cell killing , IL-1 secretion , reactive oxygen intermediate release , nitric oxide synthetase activity as measured by the release of reactive nitrogen intermediates , complement receptor-1 cell surface protein , and TNF-alpha protein presence .

<protein>Cytotoxicity markers</protein> assessed include tumor cell killing , <protein>IL-1</protein> secretion , reactive oxygen intermediate release , <protein>nitric oxide synthetase</protein> activity as measured by the release of reactive nitrogen intermediates , <protein>complement receptor-1 cell surface protein</protein> , and <protein>TNF-alpha protein</protein> presence .


Monocytes stimulated with LPS concentrations of 1.0 micrograms/ml displayed the above cytotoxic markers , whereas monocytes stimulated with DHEA alone or with LPS at a lower concentration of 0.2 ng/ml did not .

<cell_type>Monocytes</cell_type> stimulated with LPS concentrations of 1.0 micrograms/ml displayed the above cytotoxic markers , whereas <cell_type>monocytes</cell_type> stimulated with DHEA alone or with LPS at a lower concentration of 0.2 ng/ml did not .


However , when used simultaneously , DHEA and LPS 0.2 ng/ml displayed a synergistic effect on monocyte cytotoxicity against cancerous cell lines , IL-1 secretion , reactive nitrogen intermediate release , complement receptor-1 cell-surface protein , and TNF-alpha protein to levels comparable with levels obtained using LPS 1.0 microgram/ml .

However , when used simultaneously , DHEA and LPS 0.2 ng/ml displayed a synergistic effect on monocyte cytotoxicity against <cell_line>cancerous cell lines</cell_line> , <protein>IL-1</protein> secretion , reactive nitrogen intermediate release , <protein>complement receptor-1 cell-surface protein</protein> , and <protein>TNF-alpha protein</protein> to levels comparable with levels obtained using LPS 1.0 microgram/ml .


Finally , Scatchard plot analysis demonstrated the presence of a DHEA receptor in monocytes , suggesting that DHEA effects on LPS-stimulated monocytes are mediated through a receptor-dependent process .

Finally , Scatchard plot analysis demonstrated the presence of a DHEA receptor in <cell_type>monocytes</cell_type> , suggesting that DHEA effects on <cell_line>LPS-stimulated monocytes</cell_line> are mediated through a receptor-dependent process .


Interferons inhibit activation of STAT6 by interleukin 4 in human monocytes by inducing SOCS-1 gene expression .

Interferons inhibit activation of <protein>STAT6</protein> by <protein>interleukin 4</protein> in <cell_type>human monocytes</cell_type> by inducing <dna>SOCS-1 gene</dna> expression .


Interferons ( IFNs ) inhibit induction by IL-4 of multiple genes in human monocytes .

<protein>Interferons</protein> ( <protein>IFNs</protein> ) inhibit induction by <protein>IL-4</protein> of multiple genes in <cell_type>human monocytes</cell_type> .


However , the mechanism by which IFNs mediate this inhibition has not been defined .

However , the mechanism by which <protein>IFNs</protein> mediate this inhibition has not been defined .


IL-4 activates gene expression by inducing tyrosine phosphorylation , homodimerization , and nuclear translocation of the latent transcription factor , STAT6 ( signal transducer and activator of transcription-6 ) .

<protein>IL-4</protein> activates gene expression by inducing tyrosine phosphorylation , homodimerization , and nuclear translocation of the <protein>latent transcription factor</protein> , <protein>STAT6</protein> ( <protein>signal transducer and activator of transcription-6</protein> ) .


STAT6 -responsive elements are characteristically present in the promoters of IL-4-inducible genes .

<protein>STAT6</protein> -responsive elements are characteristically present in the <dna>promoters</dna> of <dna>IL-4-inducible genes</dna> .


Because STAT6 activation is essential for IL-4 -induced gene expression , we examined the ability of type I and type II IFNs to regulate activation of STAT6 by IL-4 in primary human monocytes .

Because <protein>STAT6</protein> activation is essential for <protein>IL-4</protein> -induced gene expression , we examined the ability of type I and type II <protein>IFNs</protein> to regulate activation of <protein>STAT6</protein> by <protein>IL-4</protein> in <cell_type>primary human monocytes</cell_type> .


Pretreatment of monocytes with IFN-beta or IFN-gamma , but not IL-1 , IL-2 , macrophage colony-stimulating factor , granulocyte/macrophage colony-stimulating factor , IL-6 , or transforming growth factor beta suppressed activation of STAT6 by IL-4 .

Pretreatment of <cell_type>monocytes</cell_type> with <protein>IFN-beta</protein> or <protein>IFN-gamma</protein> , but not <protein>IL-1</protein> , <protein>IL-2</protein> , <protein>macrophage colony-stimulating factor</protein> , <protein>granulocyte/macrophage colony-stimulating factor</protein> , <protein>IL-6</protein> , or transforming growth factor beta suppressed activation of <protein>STAT6</protein> by <protein>IL-4</protein> .


This inhibition was associated with decreased tyrosine phosphorylation and nuclear translocation of STAT6 and was not evident unless the cells were preincubated with IFN for at least 1 hr before IL-4 stimulation .

This inhibition was associated with decreased tyrosine phosphorylation and nuclear translocation of <protein>STAT6</protein> and was not evident unless the cells were preincubated with <protein>IFN</protein> for at least 1 hr before <protein>IL-4</protein> stimulation .


Furthermore , inhibition by IFN could be blocked by cotreatment with actinomycin D and correlated temporally with induction of the JAK/STAT inhibitory gene , SOCS-1 .

Furthermore , inhibition by <protein>IFN</protein> could be blocked by cotreatment with actinomycin D and correlated temporally with induction of the <dna>JAK/STAT inhibitory gene</dna> , <dna>SOCS-1</dna> .


Forced expression of SOCS-1 in a macrophage cell line , RAW264 , markedly suppressed trans-activation of an IL-4-inducible reporter as well as IL-6- and IFN-gamma-induced reporter gene activity .

Forced expression of <dna>SOCS-1</dna> in a <cell_line>macrophage cell line</cell_line> , <cell_line>RAW264</cell_line> , markedly suppressed trans-activation of an <dna>IL-4-inducible reporter</dna> as well as IL-6- and IFN-gamma-induced reporter gene activity .


These findings demonstrate that IFNs inhibit IL-4 -induced activation of STAT6 and STAT6 -dependent gene expression , at least in part , by inducing expression of SOCS-1 .

These findings demonstrate that <protein>IFNs</protein> inhibit <protein>IL-4</protein> -induced activation of <protein>STAT6</protein> and <protein>STAT6</protein> -dependent gene expression , at least in part , by inducing expression of <dna>SOCS-1</dna> .


An activation-responsive element in single C motif-1/lymphotactin promoter is a site of constitutive and inducible DNA-protein interactions involving nuclear factor of activated T cell .

An activation-responsive element in single <dna>C motif-1/lymphotactin promoter</dna> is a site of constitutive and inducible DNA-protein interactions involving <protein>nuclear factor of activated T cell</protein> .


Single C motif-1 ( SCM-1 ) /lymphotactin is a C-type chemokine whose expression is activation dependent , cyclosporin A sensitive and restricted to CD8+ T cells , double-negative thymocytes , gammadelta-type T cells , and NK cells .

<protein>Single C motif-1 ( SCM-1 ) /lymphotactin</protein> is a <protein>C-type chemokine</protein> whose expression is activation dependent , cyclosporin A sensitive and restricted to <cell_type>CD8+ T cells</cell_type> , <cell_type>double-negative thymocytes</cell_type> , <cell_type>gammadelta-type T cells</cell_type> , and <cell_type>NK cells</cell_type> .


In humans , there are two highly homologous genes encoding SCM-1alpha and SCM-1beta .

In humans , there are two highly <dna>homologous genes</dna> encoding <protein>SCM-1alpha</protein> and <protein>SCM-1beta</protein> .


Here we examined the regulatory mechanism of the SCM-1 genes .

Here we examined the regulatory mechanism of the <dna>SCM-1 genes</dna> .


The luciferase reporter gene under the control of the 5 ' flanking region of 0.7 kb was strongly induced upon activation with anti-CD3 or PHA plus PMA only in SCM-1-producer T cell lines through a cyclosporin A-sensitive mechanism .

The <dna>luciferase reporter gene</dna> under the control of the <dna>5 ' flanking region</dna> of 0.7 kb was strongly induced upon activation with <protein>anti-CD3</protein> or <protein>PHA</protein> plus PMA only in <cell_line>SCM-1-producer T cell lines</cell_line> through a cyclosporin A-sensitive mechanism .


An element termed E1 located at -108 to -95 nt relative to the major transcription start site was found to be critical for the promoter activity .

An element termed <dna>E1</dna> located at <dna>-108 to -95 nt</dna> relative to the major transcription start site was found to be critical for the promoter activity .


In electrophoretic mobility shift assays using the E1 oligonucleotide as probe , nuclear extracts from unstimulated T and B cell lines formed a constitutive complex termed complex I , while nuclear extracts from stimulated SCM-1-producer T cell lines formed a higher mobility complex termed complex II with a concomitant decrease in complex I .

In electrophoretic mobility shift assays using the <dna>E1</dna> oligonucleotide as probe , nuclear extracts from unstimulated T and <cell_line>B cell lines</cell_line> formed a <protein>constitutive complex</protein> termed <protein>complex I</protein> , while nuclear extracts from stimulated <cell_line>SCM-1-producer T cell lines</cell_line> formed a <protein>higher mobility complex</protein> termed <protein>complex II</protein> with a concomitant decrease in <protein>complex I</protein> .


The shift from complex I to complex II seen only in SCM-1-producer T cell lines upon activation was completely suppressed by cyclosporin A .

The shift from <protein>complex I</protein> to <protein>complex II</protein> seen only in <cell_line>SCM-1-producer T cell lines</cell_line> upon activation was completely suppressed by cyclosporin A .


Both complexes were critically dependent on the NF-AT core sequence TTTCC in the E1 element and were partially supershifted by anti-NF-ATp .

Both complexes were critically dependent on the <dna>NF-AT core sequence</dna> TTTCC in the <dna>E1 element</dna> and were partially supershifted by <protein>anti-NF-ATp</protein> .


One-hybrid assays in yeast isolated NF-ATp as an E1 binding protein , and transfection of NF-ATp into T and B cell lines strongly enhanced the activation-dependent SCM-1 promoter activity .

One-hybrid assays in <protein>yeast isolated NF-ATp</protein> as an <protein>E1 binding protein</protein> , and transfection of <protein>NF-ATp</protein> into <cell_line>T and B cell lines</cell_line> strongly enhanced the <protein>activation-dependent SCM-1</protein> promoter activity .


Collectively , a unique mechanism involving NF-ATp appears to regulate the cell type-specific and activation-dependent expression of the SCM-1 genes .

Collectively , a unique mechanism involving <protein>NF-ATp</protein> appears to regulate the cell type-specific and activation-dependent expression of the <dna>SCM-1 genes</dna> .


Dopamine stimulates expression of the human immunodeficiency virus type 1 via NF-kappaB in cells of the immune system .

Dopamine stimulates expression of the human immunodeficiency virus type 1 via <protein>NF-kappaB</protein> in cells of the immune system .


Recent studies have reported that lymphocytes produce , transport and bind dopamine present in plasma .

Recent studies have reported that <cell_type>lymphocytes</cell_type> produce , transport and bind dopamine present in plasma .


However , the action of dopamine on HIV-1 gene expression in cells of the immune system has not yet been examined .


Here , we have investigated the regulation of HIV-1 expression by dopamine in Jurkat T cells and in primary blood mononuclear cells ( PBMC ) .

Here , we have investigated the regulation of HIV-1 expression by dopamine in <cell_line>Jurkat T cells</cell_line> and in <cell_type>primary blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) .


HIV-1 replication was increased by dopamine , which correlated with the increased levels of HIV-1 transactivation .


Our transient expression data revealed that dopamine stimulated transcription through the NF-kappaB element present in the long terminal repeat .

Our transient expression data revealed that dopamine stimulated transcription through the <dna>NF-kappaB element</dna> present in the <dna>long terminal repeat</dna> .


The importance of NF-kappaB sites was confirmed by using vectors containing wild-type or mutant kappaB sites in a heterologous promoter .

The importance of <dna>NF-kappaB sites</dna> was confirmed by using vectors containing <dna>wild-type or mutant kappaB sites</dna> in a <dna>heterologous promoter</dna> .


Consistent with the role of NF-kappaB in mediating dopamine responsiveness , the proteasome inhibitor MG132 abolished dopamine-induced transcriptional activation .

Consistent with the role of <protein>NF-kappaB</protein> in mediating dopamine responsiveness , the proteasome inhibitor MG132 abolished dopamine-induced transcriptional activation .


We further explored the effect of dopamine in the presence of phorbol esters or tumor necrosis factor-alpha ( TNF-alpha ) known to activate NF-kappaB .

We further explored the effect of dopamine in the presence of phorbol esters or <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) known to activate <protein>NF-kappaB</protein> .


The combination of dopamine and TNF-alpha led to a stimulation of HIV-1 transcription and replication .

The combination of dopamine and <protein>TNF-alpha</protein> led to a stimulation of HIV-1 transcription and replication .


However , in contrast with TNF-alpha , dopamine treatment did not affect NF-kappaB DNA binding activity nor the concentrations of p50 , p65 and IkappaB-alpha proteins , which suggests a distinct NF-kappaB activation mechanism .

However , in contrast with <protein>TNF-alpha</protein> , dopamine treatment did not affect <protein>NF-kappaB</protein> DNA binding activity nor the concentrations of <protein>p50</protein> , <protein>p65</protein> and <protein>IkappaB-alpha proteins</protein> , which suggests a distinct <protein>NF-kappaB</protein> activation mechanism .


These results reveal a new link between the dopamine system , cytokine signaling pathway and regulation of gene expression via the involvement of NF-kappaB in T cells and PBMC .

These results reveal a new link between the dopamine system , <protein>cytokine</protein> signaling pathway and regulation of gene expression via the involvement of <protein>NF-kappaB</protein> in <cell_type>T cells</cell_type> and <cell_type>PBMC</cell_type> .


[ Hormonal metabolic status in breast cancer patients after conservative surgery : comparison with known prognostic criteria ]


Body weight , body mass index , body fat , lean body mass , blood-glucose , cholesterol , HDL-cholesterol , triglyceride , beta-lipoproteins , insulin , gonadotropin , estradiol , testosterone , SHBG , T3 , T4 and TSH levels as well as estradiol and progesterone receptor levels in excised tumor were studied in 40 patients with breast cancer prior to conservative treatment .

Body weight , body mass index , body fat , lean body mass , blood-glucose , cholesterol , <protein>HDL-cholesterol</protein> , triglyceride , <protein>beta-lipoproteins</protein> , insulin , gonadotropin , estradiol , testosterone , <protein>SHBG</protein> , <protein>T3</protein> , <protein>T4</protein> and TSH levels as well as estradiol and progesterone receptor levels in excised tumor were studied in 40 patients with breast cancer prior to conservative treatment .


Said anthropometric , metabolic and hormonal parameters were compared with the index of lymphocytic infiltration of tumor selected as a prognostic factor .


A significant correlation between high lymphocytic infiltration ( 2.5 points ) , low body mass and fat was identified .


Also , smoking contributed to loss of body mass and fat ; however , it caused lymphocytic infiltration to rise .


Moderate body mass , relatively low fat level and positive receptor status are among factors of good prognosis in breast cancer of early stages .


Selective DNA-binding activity of interleukin-10-stimulated STAT molecules in human monocytes .

Selective DNA-binding activity of <protein>interleukin-10-stimulated STAT molecules</protein> in <cell_type>human monocytes</cell_type> .


It has been demonstrated that interferon-gamma ( IFN-gamma ) and interleukin-10 ( IL-10 ) have various reverse effects on macrophages ; however , the molecular mechanism of this difference has not been fully understood .

It has been demonstrated that <protein>interferon-gamma</protein> ( <protein>IFN-gamma</protein> ) and <protein>interleukin-10</protein> ( <protein>IL-10</protein> ) have various reverse effects on <cell_type>macrophages</cell_type> ; however , the molecular mechanism of this difference has not been fully understood .


In this study , we analyzed the binding activity of IL-10- and IFN-gamma-activated STAT molecules to two kinds of GAS -motif sequences .

In this study , we analyzed the binding activity of <protein>IL-10- and IFN-gamma-activated STAT molecules</protein> to two kinds of <dna>GAS</dna> -motif sequences .


IL-10-activated STAT1 could bind to the GAS-motif sequence in the promoter region of the Fcgamma receptor , but not to that in the promoter region of the COX-2 gene , whereas IFN-gamma-activated STAT1 and STAT5 could bind to both sequences .

<protein>IL-10-activated STAT1</protein> could bind to the <dna>GAS-motif sequence</dna> in the promoter region of the <protein>Fcgamma receptor</protein> , but not to that in the <dna>promoter region</dna> of the <dna>COX-2 gene</dna> , whereas <protein>IFN-gamma-activated STAT1</protein> and <protein>STAT5</protein> could bind to both sequences .


IL-10 inhibited IFN-gamma -induced STAT activation without newly synthesized protein .

<protein>IL-10</protein> inhibited <protein>IFN-gamma</protein> -induced <protein>STAT</protein> activation without <protein>newly synthesized protein</protein> .


We further demonstrated that aspirin , but not dexamethasone , suppressed IFN-gamma -induced STAT activation .

We further demonstrated that aspirin , but not dexamethasone , suppressed <protein>IFN-gamma</protein> -induced <protein>STAT</protein> activation .


Taken together , these results suggest that IL-10-activated STAT1 has a specificity in binding to the GAS-motif sequences , whereas IFN-gamma-activated STAT1 and STAT5 have a broader spectrum in binding to the GAS-motif sequences .

Taken together , these results suggest that <protein>IL-10-activated STAT1</protein> has a specificity in binding to the <dna>GAS-motif sequences</dna> , whereas <protein>IFN-gamma-activated STAT1</protein> and <protein>STAT5</protein> have a broader spectrum in binding to the <dna>GAS-motif sequences</dna> .


This may explain the difference between IL-10 and IFN-gamma in biological activity , and the inhibitory effect of IL-10 on IFN-gamma activities .

This may explain the difference between <protein>IL-10</protein> and <protein>IFN-gamma</protein> in biological activity , and the inhibitory effect of <protein>IL-10</protein> on <protein>IFN-gamma</protein> activities .


Peptide binding affinity and pH variation establish functional thresholds for activation of HLA-DQ -restricted T cell recognition .

Peptide binding affinity and pH variation establish functional thresholds for activation of <dna>HLA-DQ</dna> -restricted T cell recognition .


Peptides derived from the HSV-2 VP16 protein were utilized for studies of peptide binding to DQ0302 molecules and T cell activation at both neutral and acidic pH .

Peptides derived from the <protein>HSV-2 VP16 protein</protein> were utilized for studies of peptide binding to DQ0302 molecules and T cell activation at both neutral and acidic pH .


The native peptide VP16 430-444 contains an Asp at position 442 , binds to DQ0302 strongly , with a Kd value of 50nM at acidic pH and very weakly , with a Kd value of greater than 10 microM at neutral pH .

The native peptide VP16 430-444 contains an Asp at <protein>position 442</protein> , binds to DQ0302 strongly , with a Kd value of 50nM at acidic pH and very weakly , with a Kd value of greater than 10 microM at neutral pH .


A truncated version of 430-444 , i.e. , VP16 433-442 , binds with an affinity 10-fold lower compared to 430-444 at acidic pH , and binding at neutral pH was barely detectable .


The homologous peptide 430-444 , 442A has an Asp to Ala substitution at position 442 and binds to DQ0302 with a Kd similar to 433-442 .


The short truncated analog 433-442A binds very poorly at both acidic and neutral pH .


Both the wild type 430-444 and 433-442 peptides stimulated a HSV-specific T cell clone after a brief incubation with antigen presenting cells ( APC ) expressing DQ0302 at acidic pH .

Both the wild type 430-444 and 433-442 peptides stimulated a HSV-specific T cell clone after a brief incubation with <cell_type>antigen presenting cells</cell_type> ( <cell_type>APC</cell_type> ) expressing DQ0302 at acidic pH .


Much higher concentrations of wild type peptides were needed to activate T cells at neutral pH .

Much higher concentrations of wild type peptides were needed to activate <cell_type>T cells</cell_type> at neutral pH .


In contrast , APC pulsed with Ala-substituted peptides 430-444 , 442A or 433-442A at neutral pH failed to stimulate the T cell clone , while APC pulsed at acidic pH and subsequently washed led to successful T cell activation .

In contrast , <cell_type>APC</cell_type> pulsed with Ala-substituted peptides 430-444 , 442A or 433-442A at neutral pH failed to stimulate the <cell_line>T cell clone</cell_line> , while <cell_type>APC</cell_type> pulsed at acidic pH and subsequently washed led to successful T cell activation .


The Ala-substituted peptide was recognized by the T cell clone at neutral pH only when it was present in the APC culture throughout the stimulation process .

The Ala-substituted peptide was recognized by the <cell_line>T cell clone</cell_line> at neutral pH only when it was present in the <cell_line>APC culture</cell_line> throughout the stimulation process .


While the MHC-peptide complexes formed with the native peptide are stable , complexes formed with the Ala-substituted peptide had a functional t1/2 of less than 4 hr at neutral pH .

While the <protein>MHC-peptide complexes</protein> formed with the native peptide are stable , complexes formed with the Ala-substituted peptide had a functional t1/2 of less than 4 hr at neutral pH .


ETS transcription factors regulate an enhancer activity in the third intron of TNF-alpha .

<protein>ETS transcription factors</protein> regulate an enhancer activity in the <dna>third intron</dna> of <protein>TNF-alpha</protein> .


We describe an enhancer site in the third intron of tumor necrosis factor alpha ( TNF-alpha ) .

We describe an enhancer site in the <dna>third intron</dna> of <protein>tumor necrosis factor alpha</protein> ( <protein>TNF-alpha</protein> ) .


A reporter construct containing the 5'-flanking region of the mouse TNF-alpha gene displayed weak activity when transfected into RAW264.7 macrophage-like cells .

A <dna>reporter construct</dna> containing the <dna>5'-flanking region</dna> of the mouse <dna>TNF-alpha gene</dna> displayed weak activity when transfected into <cell_line>RAW264.7 macrophage-like cells</cell_line> .


The addition of the third intron of TNF-alpha to this construct resulted in an enhancement of CAT protein .

The addition of the <dna>third intron</dna> of <protein>TNF-alpha</protein> to this construct resulted in an enhancement of <protein>CAT protein</protein> .


This enhancement was eliminated if a conserved 20-bp sequence was removed from the intron or if a dominant-negative ets-binding factor was co-transfected with the reporter gene .

This enhancement was eliminated if a <dna>conserved 20-bp sequence</dna> was removed from the <dna>intron</dna> or if a <protein>dominant-negative ets-binding factor</protein> was co-transfected with the <dna>reporter gene</dna> .


Mutations of this site that destroyed potential ets transcription factor binding sites had reduced transcriptional activity .

Mutations of this site that destroyed potential <dna>ets transcription factor binding sites</dna> had reduced transcriptional activity .


The major transcription factor that bound to the oligonucleotide was confirmed to be GABP by supershift and competition analysis .

The major transcription factor that bound to the oligonucleotide was confirmed to be <protein>GABP</protein> by supershift and competition analysis .


In RAW264.7 cells , the binding was constitutive , however , in bone marrow-derived macrophages binding activity was shown to be interferon-gamma inducible .

In <cell_line>RAW264.7 cells</cell_line> , the binding was constitutive , however , in <cell_line>bone marrow-derived macrophages</cell_line> binding activity was shown to be <protein>interferon-gamma</protein> inducible .


This may imply a role for ets transcription factors in the production of TNF-alpha .

This may imply a role for <protein>ets transcription factors</protein> in the production of <protein>TNF-alpha</protein> .


E2F-1 blocks terminal differentiation and causes proliferation in transgenic megakaryocytes .

<protein>E2F-1</protein> blocks terminal differentiation and causes proliferation in <cell_type>transgenic megakaryocytes</cell_type> .


The transcription factor E2F-1 plays a central role in the cell cycle through its ability to activate genes involved in cell division .

The <protein>transcription factor</protein> <protein>E2F-1</protein> plays a central role in the cell cycle through its ability to <dna>activate genes</dna> involved in cell division .


E2F-1 activity is regulated by a number of proteins , including the retinoblastoma susceptibility gene product , cyclin-dependent kinases , and their inhibitors , proteins that have been implicated in the control of certain developmental processes .

<protein>E2F-1</protein> activity is regulated by a number of proteins , including the retinoblastoma <dna>susceptibility gene</dna> product , <protein>cyclin-dependent kinases</protein> , and their inhibitors , proteins that have been implicated in the control of certain developmental processes .


To investigate a potential role of E2F-1 in differentiation , we assayed the ability of megakaryocytes to form platelets in an in vivo transgenic model .

To investigate a potential role of <protein>E2F-1</protein> in differentiation , we assayed the ability of <cell_type>megakaryocytes</cell_type> to form <cell_type>platelets</cell_type> in an in vivo transgenic model .


E2F-1 expression in megakaryocytes blocked differentiation during maturation , resulting in severe thrombocytopenia .

<protein>E2F-1</protein> expression in <cell_type>megakaryocytes</cell_type> blocked differentiation during maturation , resulting in severe thrombocytopenia .


Ultrastructural analysis of megakaryocytes revealed abnormal development characterized by hyperdemarcation of cytoplasmic membranes and reduced numbers of alpha granules .

Ultrastructural analysis of <cell_type>megakaryocytes</cell_type> revealed abnormal development characterized by hyperdemarcation of cytoplasmic membranes and reduced numbers of alpha granules .


Administration of megakaryocyte growth and development factor or interleukin 6 could not overcome the differentiation block .

Administration of <protein>megakaryocyte growth and development factor</protein> or <protein>interleukin 6</protein> could not overcome the differentiation block .


Additionally , E2F-1 caused massive megakaryocyte accumulation in both normal and ectopic sites , first evident in E15 embryonic liver .

Additionally , <protein>E2F-1</protein> caused massive <cell_type>megakaryocyte</cell_type> accumulation in both normal and ectopic sites , first evident in E15 embryonic liver .


Furthermore , significant apoptosis was observed in transgenic megakaryocytes .

Furthermore , significant apoptosis was observed in <cell_type>transgenic megakaryocytes</cell_type> .


These data indicate that E2F-1 can prevent terminal differentiation , probably through its cell cycle-stimulatory activity .

These data indicate that <protein>E2F-1</protein> can prevent terminal differentiation , probably through its cell cycle-stimulatory activity .


Polymorphic nucleotides within the human IL-4 promoter that mediate overexpression of the gene .

Polymorphic nucleotides within the <dna>human IL-4 promoter</dna> that mediate overexpression of the gene .