Transcription factor activation Transcription factor activation in lymphokine activated killer cells and lymphocytes from patients receiving IL-2 immunotherapy . the TF site In vitro binding studies demonstrated that the TF site bound translated c-Rel and p65 homodimers but not p50\/p65 heterodimers or p50 homodimers . Spi-B Gel-retardation experiments show that Spi-B can bind to all putative PU.1 binding sites , but do not reveal any preferred Spi-B binding site . pRb p130 , predominantly in Form 1 , and hypophosphorylated pRb bind an E2F DNA binding site ; p130 complexes E2F-4 , whereas pRb binds both E2F-4 and E2F-1 . this paired motif We find that HMG-I binds preferentially to the more 3' of a pair of GATA motifs in the gamma-globin promoter ; this paired motif is bound by the erythroid factor GATA-1 . GGGACTTTCC The kappa B sequence ( GGGACTTTCC ) binds a factor , NF-kappa B , that is constitutively found in its functional , DNA binding form only in B lymphocytes . The IL-2R alpha enhancer The IL-2R alpha enhancer binds NF-kappa B poorly and is only weakly activated by the NF-kappa B site alone . The kappa B sequence The kappa B sequence ( GGGACTTTCC ) binds a factor , NF-kappa B , that is constitutively found in its functional , DNA binding form only in B lymphocytes . three sites Although three sites in the TNF-alpha promoter ( kappa 1 , kappa 2 , and kappa 3 ) specifically bind the transcription factor NF-kappa B in lymphoid nuclear extracts , TNF-alpha mRNA induction by PMA does not correlate with NF-kappa B binding activities displayed by different T and B cell lines . IL-4 IL-4 down-regulates IL-2- , IL-3- , and GM-CSF-induced cytokine gene expression in peripheral blood monocytes . a tyrosine kinase inhibitor Furthermore , both transforming growth factor-beta and genistein , a tyrosine kinase inhibitor , could suppress IL-2 and IL-12 signaling but CsA was generally inactive . genistein Furthermore , both transforming growth factor-beta and genistein , a tyrosine kinase inhibitor , could suppress IL-2 and IL-12 signaling but CsA was generally inactive . transforming growth factor-beta Furthermore , both transforming growth factor-beta and genistein , a tyrosine kinase inhibitor , could suppress IL-2 and IL-12 signaling but CsA was generally inactive . 4 hours We identified a cell-type-specific differential response : CREB , CTF , OTF-1 , OFT-2 , and NF-kappa B genes were strongly induced 1 to 4 hours after influenza A virus infection in the monocytic cell line Mono Mac 6 , while in freshly prepared human monocytes no significant changes were detected . ATRA treatment of Kasumi-1 cells Consistent with these findings , VD-responsive genes are induced by ATRA treatment of Kasumi-1 cells , suggesting that the genetic program underlying monocytic differentiation is activated . Stable expression a diverged homeobox human gene Stable expression of HB24 , a diverged human homeobox gene , in T lymphocytes induces genes involved in T cell activation and growth . Stable expression of HB24 Stable expression of HB24 , a diverged human homeobox gene , in T lymphocytes induces genes involved in T cell activation and growth . TPA Other studies further demonstrate that the jun-B and fra-1 genes are induced by TPA in both HL-60\/vinc and HL-60\/vinc\/R cells , whereas c-fos expression is attenuated in the HL-60\/vinc line . lipopolysaccharide lp We and others have shown that SAA gene is induced in monocyte\/macrophage cells by lipopolysaccharide ( LPS ) . AP-1 In contrast , AP-1 from PHA-activated cells contains c-Jun and low levels of c-Fos . The AP-1 binding protein The AP-1 binding proteins contained c-Jun , Jun-D , and Fra-1 , but marginal amounts of Jun-B and c-Fos . that Gel-shift analysis reveals the constitutive presence of nuclear factors in resting PBL that bind to the proximal AP-1 site of the IL-2 promoter and that contain immunoreactive c-Jun but not c-Fos protein . the kappa 3 binding factor Here , we demonstrate that the kappa 3 binding factor contains NFATp , a cyclosporin-sensitive DNA-binding protein required for interleukin-2 gene transcription . fresh ATL samples Whereas the NF-kappaB binding activity in Tax-expressing T-cell lines consisted mostly of p50\/c-Rel , fresh ATL samples contained p50\/p50 and p50\/p65 heterodimers . the nucleoprotein complex Electrophoretic mobility shift assays show that the nucleoprotein complex formed on the upstream site ( NF kappa B1 ) contains the classical p50\/p65 heterodimer . Western-blot analysis of the sedimentation peak Western-blot analysis of the sedimentation peak showed the concomitant presence of MBP-HBD by a monoclonal anti-MBP antibody , and hsp90 by a monoclonal anti-hsp antibody . One cDNA clone of a primary response gene One cDNA clone of a primary response gene , expressed upon macrophage differentiation , encoded for Egr-1 , a zinc finger transcription factor . 4 hours We identified a cell-type-specific differential response : CREB , CTF , OTF-1 , OFT-2 , and NF-kappa B genes were strongly induced 1 to 4 hours after influenza A virus infection in the monocytic cell line Mono Mac 6 , while in freshly prepared human monocytes no significant changes were detected . Fc gamma R cross-linking In THP-1 cells , Fc gamma R cross-linking induced NF-kappa B , which is known to bind to the regulatory region of the long terminal repeat ( LTR ) of HIV-1 and to activate HIV-1 transcription . IL-2 In addition , IL-2 but not IL-12 induced nuclear factors NF-kappa B and AP1 , and regulation of the nuclear levels of these two DNA binding protein complexes is correlated with IFN-gamma and GM-CSF gene expression . PMA Double-stimulation was used to demonstrate that , in a T lymphocytic cell line ( CEM ) , phorbol myristate acetate ( PMA ) rapidly induced NF-kappa B through a signaling pathway which did not involve reactive oxygen species ( ROS ) and was different from the activation triggered by either H2O2 or tumor necrosis factor-alpha ( TNF-alpha ) . T. pallidum lipoproteins-lipopeptides Finally , the biological relevance of the observation that T. pallidum lipoproteins-lipopeptides induce both NF-kappa B and cytokine production in monocytes was supported by the ability of the synthetic analogs to promote human immunodeficiency virus replication in chronically infected U1 monocytoid cells ; these observations also suggest a potential mechanism whereby a syphilitic chancre can serve as a cofactor for human immunodeficiency virus transmission . myristate phorbol acetate Double-stimulation was used to demonstrate that , in a T lymphocytic cell line ( CEM ) , phorbol myristate acetate ( PMA ) rapidly induced NF-kappa B through a signaling pathway which did not involve reactive oxygen species ( ROS ) and was different from the activation triggered by either H2O2 or tumor necrosis factor-alpha ( TNF-alpha ) . anergized CD4 cells In vivo anergized CD4+ T cells express perturbed AP-1 and NF-kappa B transcription factors . anergized T cells In vivo anergized CD4+ T cells express perturbed AP-1 and NF-kappa B transcription factors . ALD We had previously found that aspirin-like drugs ( ALD ) induce AP-1 in human T lymphocytes . B7 costimulation LFA-3 induced moderate levels of AP-1 , but did not influence the levels of NF-kappa B , while B7 costimulation strongly induced both AP-1 and substantially enhanced NF-kappa B binding proteins . B7 stimulation However , subsequent analysis of transcription factor generation revealed that B7 stimulation induced both activator protein-1 ( AP-1 ) and nuclear factor-kappaB ( NF-kappaB ) complexes , but not NF-AT . aspirin-like drugs We had previously found that aspirin-like drugs ( ALD ) induce AP-1 in human T lymphocytes . PMA TG plus phorbol myristate acetate ( PMA ) but not TG alone induced IL-2 in Jurkat T cells , suggesting that TG had no effect on protein kinase C ( PKC ) . TG TG plus phorbol myristate acetate ( PMA ) but not TG alone induced IL-2 in Jurkat T cells , suggesting that TG had no effect on protein kinase C ( PKC ) . myristate phorbol acetate TG plus phorbol myristate acetate ( PMA ) but not TG alone induced IL-2 in Jurkat T cells , suggesting that TG had no effect on protein kinase C ( PKC ) . phorbol myristate acetate PMA stimulation These B cells expressed p40 and p35 mRNA , and phorbol myristate acetate ( PMA ) stimulation strongly enhanced p40 and p70 production . ADP-activated platelets In addition , ADP-activated platelets induced MCP-1 and ICAM-1 promoter-dependent transcription . Binding of activated platelets Binding of activated platelets induces IL-1 beta , IL-8 , and MCP-1 in leukocytes . which The latter class of events is blocked in lymphocytes by the immunosuppressive drugs cyclosporin A and FK506 , which inhibit calcineurin , a Ca2+-activated serine\/threonine phosphatase necessary for the nuclear import of NF-AT transcription factors . IL-4 IL-4 down-regulates IL-2- , IL-3- , and GM-CSF-induced cytokine gene expression in peripheral blood monocytes . a tyrosine kinase inhibitor Furthermore , both transforming growth factor-beta and genistein , a tyrosine kinase inhibitor , could suppress IL-2 and IL-12 signaling but CsA was generally inactive . genistein Furthermore , both transforming growth factor-beta and genistein , a tyrosine kinase inhibitor , could suppress IL-2 and IL-12 signaling but CsA was generally inactive . transforming growth factor-beta Furthermore , both transforming growth factor-beta and genistein , a tyrosine kinase inhibitor , could suppress IL-2 and IL-12 signaling but CsA was generally inactive . Forced expression of SOCS-1 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 . RAW264 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 . Combined treatment of HPCs Combined treatment of HPCs with alpha-PML and alpha-Rb oligomers inhibited both PML and Rb protein expression and completely blocked erythroid colony development . NAC Monocytic cell adhesion to EC in response to tumor necrosis factor-alpha ( TNF-alpha ) , lipopolysaccharide ( LPS ) , alpha-thrombin , or phorbol 12-myristate 13-acetate ( PMA ) was similarly inhibited by NAC . T cell activation signals In conclusion , HIV-1 and HIV-2 are differentially regulated by T cell activation signals , and this difference may account for the longer period of viral latency observed with HIV-2 than with HIV-1 infection . we In a subject with primary cortisol resistance we have observed glucocorticoid receptors ( hGR ) with a decreased affinity for dexamethasone . Interleukin-10 Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma-induced genes by suppressing tyrosine phosphorylation of STAT1 . other cytokines Therefore , the effects of PGE2 vary depending on the mode of T cell activation , and the IL-4 and IL-5 are regulated differently from other cytokines . the IL-12-dependent transactivation of an IRF-1 reporter construct First , STAT4 was required for the IL-12-dependent transactivation of an IRF-1 reporter construct , and second , STAT4 binding to the IRF-1 promoter was shown using EMSA . I kappa b alpha In contrast to hematopoietic cells , I kappa B alpha-\/- embryonic fibroblasts show minimal constitutive NF-kappa B , as well as normal signal-dependent NF-kappa B activation that is concomitant with I kappa B beta degradation . AIDS-C patients AIDS-C patients showed low IL-2 and high IL-4 , IL-10 , and IgE concentratios ; conversely , AIDS-GR patients showed high IL-2 and low IL-4 and IgE concentrations . AIDS-GR patients AIDS-C patients showed low IL-2 and high IL-4 , IL-10 , and IgE concentratios ; conversely , AIDS-GR patients showed high IL-2 and low IL-4 and IgE concentrations . I kappa b alpha In contrast to hematopoietic cells , I kappa B alpha-\/- embryonic fibroblasts show minimal constitutive NF-kappa B , as well as normal signal-dependent NF-kappa B activation that is concomitant with I kappa B beta degradation . histopathological analysis To further unravel the tal-1 oncogenic potential , a strain of tal-1 transgenic mice was crossbred with p53-\/- mice ; the survival rate in these animals was reduced by more than one-half when compared with that of tal-1 mice , and histopathological analysis revealed exclusively T-cell lymphomas . We We evaluated two cytokine systems , IL-2 and IFNgamma , and demonstrate that Nmi augments STAT-mediated transcription in response to these cytokines . We We evaluated 49 female patients with MPD and informative at the X-linked androgen receptor ( AR ) locus to establish the X chromosome inactivation pattern of hemopoietic cells . JNK Similarly , IL-2 neither activates JNK nor increases AP-1 binding activity to a consensus o-tetradecanoylphorbol 13-acetate ( TPA ) response element . PI3K Phosphatidyl inositol 3-kinase ( PI3K ) is activated by IL-2 . Phosphatidyl inositol 3-kinase Phosphatidyl inositol 3-kinase ( PI3K ) is activated by IL-2 . STAT1 alpha Although IL-2 and IFN-alpha activated STAT1 alpha and STAT5 , IL-2 predominantly activated STAT5 , while IFN-alpha predominantly activated STAT1 alpha . STAT5 Although IL-2 and IFN-alpha activated STAT1 alpha and STAT5 , IL-2 predominantly activated STAT5 , while IFN-alpha predominantly activated STAT1 alpha . Stat3 Interleukin-2 ( IL-2 ) rapidly activated Stat5 in fresh PBL , and Stat3 and Stat5 in preactivated PBL . Stat3alpha As determined by tyrosine phosphorylation , nuclear translocation and binding to an hSIE-oligonucleotide probe , IL-2 and IL-15 activated the slowly migrating isoform , Stat3alpha . Stat3alpha In contrast , minimal or no activation of Stat3beta was observed , suggesting that IL-2 and IL-15 predominantly activate Stat3alpha in human CD4(+) T cells . Stat5 Interleukin-2 ( IL-2 ) rapidly activated Stat5 in fresh PBL , and Stat3 and Stat5 in preactivated PBL . Stat5 Prolactin activates Stat5 , and interleukin-4 ( IL-4 ) activates Stat6 . nf-kappa b Similarly , IL-2 activates NF-kappa B in the human monocytic cell line U 937 , but not in resting human T-cells . the migrating isoform As determined by tyrosine phosphorylation , nuclear translocation and binding to an hSIE-oligonucleotide probe , IL-2 and IL-15 activated the slowly migrating isoform , Stat3alpha . many immunoregulatory genes Because NF-kappa B activates many immunoregulatory genes in response to pro-inflammatory stimuli , the inhibition of its activity can be a major component of the anti-inflammatory activity of glucocorticoids . the E-selectin promoter CsA also suppressed E-selectin , but not vascular cell adhesion molecule-1 ( VCAM-1 ) expression in endothelial cells , even though the E-selectin promoter is activated by NF-kappa B rather than NFAT . the expression of gene many Although NF-kappa B activates the expression of many genes involved in immune and inflammatory responses , little is known about the role of NF-kappa B activation in the induction of IgE synthesis in human B cells . These enhancer regions These promoter and enhancer regions are mainly activated by the transcription factor nuclear factor of activated T cells ( NFAT ) . These promoter regions These promoter and enhancer regions are mainly activated by the transcription factor nuclear factor of activated T cells ( NFAT ) . porcine EC in We have previously demonstrated that human NK cells activate porcine EC in vitro , which results in adhesion molecule expression and cytokine secretion . ligands The T cell surface molecule CD28 binds to ligands on accessory cells and APCs , playing an important costimulatory role in the response of T cells to Ags . the GR Cortisol and various synthetic glucocorticoids bind to the GR with one-site kinetics . receptors Both IL-2 and IL-4 bind to receptors containing the common gamma chain and JAK3 . receptors Both IL-2 and IL-4 bind to receptors containing the common gamma chain and JAK3 . B-cell activation Cyclosporin A and FK506 inhibit T- and B-cell activation and other processes essential to an effective immune response . NFAT activation With these clones , we demonstrated that NFAT activation induced by phorbol 12-myristate 13-acetate and ionomycin was inhibited by both cyclosporin A ( CsA ) ( IC50 = 8 nM ) and FK506 ( IC50 = 160 pM ) , presumably by inhibition of calcineurin activity . T Cyclosporin A and FK506 inhibit T- and B-cell activation and other processes essential to an effective immune response . The activation of calcineurin of NF-ATc The activation of calcineurin and the nuclear import of NF-ATc can both be blocked by cyclosporin A or FK506 in complex with their respective immunophilins . The activation the nuclear import of NF-ATc The activation of calcineurin and the nuclear import of NF-ATc can both be blocked by cyclosporin A or FK506 in complex with their respective immunophilins . other processes essential Cyclosporin A and FK506 inhibit T- and B-cell activation and other processes essential to an effective immune response . the PMA\/ionomycin-induced activation Furthermore , we confirmed the previous report that FK506 suppressed the PMA\/ionomycin-induced activation through authentic kappa B site of immunoglobulin ( Ig ) gene , to which NF-kappa B binding was also decreased by FK506 , indicating that both IL-8 kappa B-like site and Ig kappa B site are FK506-sensitive in spite of the difference of binding factors . the activating function of p95vav Furthermore , the activating function of p95vav is blocked by FK506 , suggesting that its activity also depends on calcineurin . the appearance of DNA binding activity of factors However , CsA and FK506 inhibit the appearance of DNA binding activity of factors that bind to the NF-AT and AP-1 sites in the IL-2 enhancer . the effect of SML cytosol of FKBP51 A role for changes in immunophilins , causing glucocorticoid resistance in neotropical primates , is supported by the following : the changes in FKBP51 and FKBP52 were observed in cells from other neotropical primates with glucocorticoid resistance ; the elevated level of FKBP51 was reflected in an abundance of FKBP51 in heat shock protein 90 complexes in SML ; when cytosols of SML and L929 cells were mixed , the decrease in GR binding was associated with incorporation of FKBP51 into GR heterocomplexes ; the effect of SML cytosol on GR binding was reproduced with cytosol from COS cells expressing squirrel monkey FKBP51 ; and both the effect of SML cytosol on GR binding and the incorporation of FKBP51 into GR heterocomplexes were blocked by FK506 . the production of IL-2 Cyclosporin A ( CsA ) and FK506 inhibit the production of IL-2 in T lymphocytes at the level of gene transcription . the production of several cytokines FK506 , an immunosuppressant , inhibits the production of several cytokines in T lymphocytes . the transcription IL-8 We observed that FK506 suppressed the transcription of a chemotactic cytokine , interleukin-8 ( IL-8 ) in a human T cell line , Jurkat cells , activated by phorbol 12-myristate 13-acetate ( PMA ) and calcium ( Ca2+ ) ionophore ( ionomycin ) . the transcription Jurkat cell activate We observed that FK506 suppressed the transcription of a chemotactic cytokine , interleukin-8 ( IL-8 ) in a human T cell line , Jurkat cells , activated by phorbol 12-myristate 13-acetate ( PMA ) and calcium ( Ca2+ ) ionophore ( ionomycin ) . the transcription interleukin-8 We observed that FK506 suppressed the transcription of a chemotactic cytokine , interleukin-8 ( IL-8 ) in a human T cell line , Jurkat cells , activated by phorbol 12-myristate 13-acetate ( PMA ) and calcium ( Ca2+ ) ionophore ( ionomycin ) . the transcription of a chemotactic cytokine We observed that FK506 suppressed the transcription of a chemotactic cytokine , interleukin-8 ( IL-8 ) in a human T cell line , Jurkat cells , activated by phorbol 12-myristate 13-acetate ( PMA ) and calcium ( Ca2+ ) ionophore ( ionomycin ) . the transcriptions FK506 suppressed the transcriptions through the AP-1 or kappa B-like sites induced by PMA plus Ca(2+)-mobilizing agents , but not those induced by Ca(2+)-independent stimuli . transcription Using constructs in which mRNA production controlled by a specific transcription factor could be readily measured we found that both cyclosporin A and FK506 completely inhibited transcription activated by NF-AT , NFIL2 A , NFIL2 B and partially inhibited transcription activated by NF kappa B . transcriptional activation Cyclosporin A and FK506 inhibited only transcriptional activation that was dependent on Ca2+ mobilization . translocation of the cytoplasmic component FK506 and cyclosporin A block translocation of the cytoplasmic component without affecting synthesis of the nuclear subunit . NFAT1 Activated primed CD4 T cells contain more NFAT1 and support greater NFAT-directed transcription than unprimed CD4 T cells , while activator protein 1 binding and activator protein 1-mediated transcription by both cell types is similar . IL-2 receptor alpha gene transcription We have shown that interleukin-1 ( IL-1 ) and IL-2 control IL-2 receptor alpha ( IL-2R alpha ) gene transcription in CD4-CD8- murine T lymphocyte precursors . IL-2R alpha gene transcription We have shown that interleukin-1 ( IL-1 ) and IL-2 control IL-2 receptor alpha ( IL-2R alpha ) gene transcription in CD4-CD8- murine T lymphocyte precursors . Transcriptional control of the IL-5 gene IL-5 synthesis Transcriptional control of the IL-5 gene by human helper T cells : IL-5 synthesis is regulated independently from IL-2 or IL-4 synthesis . the cellular distribution of Aiolos Indirect immunofluorescence shows that IL-2 controls the cellular distribution of Aiolos and induces its tyrosine phosphorylation , required for dissociation from Ras . transcription Interleukin-1 and interleukin-2 control transcription via distinct cis-acting elements . transcription of gene different The exact mechanism by which IL-2 regulates transcription of different genes is presently unknown . I kappa B alpha\/MAD -3 gene transcription The demonstration that NF-kappa B can regulate I kappa B alpha\/MAD-3 gene transcription in other cell types suggested that the rapid increase in steady-state I kappa B alpha\/MAD-3 mRNA levels we observed within 30 min of monocyte adherence would result from NF-kappa B-dependent transcriptional stimulation of the I kappa B alpha\/MAD-3 gene . each other We propose a model in which NF-kappa B and I kappa B-alpha mutually regulate each other in a cycle : saturating amounts of the inhibitory I kappa B-alpha protein are destroyed upon stimulation , allowing rapid activation of NF-kappa B . expression of inhibitor kappa i b alpha NF-kappa B controls expression of inhibitor I kappa B alpha : evidence for an inducible autoregulatory pathway . the NF-kappa B1 gene Previously , we and others have demonstrated that NF-kappa B regulates the NF-kappa B1 gene . the activation of lymphocyte T The transcription factor NF-kappa B controls the induction of numerous cytokine promoters during the activation of T lymphocytes . the expression of kappa i b alpha Together , these results show that NF-kappa B controls the expression of I kappa B alpha by means of an inducible autoregulatory pathway . the induction of numerous cytokine promoters The transcription factor NF-kappa B controls the induction of numerous cytokine promoters during the activation of T lymphocytes . genes These data suggest that L. pneumophila possesses a growth phase-dependent resistance to stress that is independent of RpoS control and that RpoS likely regulates genes that enable it to survive in the environment within protozoa . any effect Furthermore , neither IL-10 nor IL-4 showed any effect on I-kappa B mRNA expression as determined by Northern experiments . no effect Binding activity of NF-IL6 was also strongly inhibited by IL-4 whereas IL-10 showed no effect . Ca2 Normal T lymphocytes whose surface expression of CD3 was depleted showed impaired UV-induced tyrosine phosphorylation and Ca2+ signals . a greater proliferation rate RESULTS : Cord lymphocytes revealed a greater proliferation rate with PHA and alphaCD3 than adult lymphocytes ( p = 0.0081 and 0.0023 , respectively ) . a significant diminished proliferation capacity Phytohemagglutinin stimulated lymphocytes derived from DS subjects showed a statistically significant diminished proliferation capacity in comparison with lymphocytes derived from NCL and healthy individuals . a significant reduction In contrast , activated T lymphocytes from older individuals show a significant reduction in the induction of NF kappa B in response to the same stimuli . an early hyperpolarization Human T and B lymphocytes demonstrate an early and transient hyperpolarization after ligand binding . an equivalent increase Adult lymphocytes showed an equivalent increase in mRNA expression of c-fos and c-jun ( 140+\/-25 and 155+\/-31 % ) at 30 min post-PHA stimulation , while cord lymphocyte maximum c-fos and c-jun expression ( 82+\/-6 and 142+\/-12 % ) occurred at 15 min post-PHA stimulation ( c-fos , p = 0.0354 ; c-jun , p = 0.0112 ) . an expression < fmol\/mg The ZR-75-1 cell line showed an expression of 642 fmol\/mg whereas lymphocytes of pregnant women showed an expression < or = 4 fmol\/mg . an expression = fmol\/mg The ZR-75-1 cell line showed an expression of 642 fmol\/mg whereas lymphocytes of pregnant women showed an expression < or = 4 fmol\/mg . an transient hyperpolarization Human T and B lymphocytes demonstrate an early and transient hyperpolarization after ligand binding . equivalent levels Lymphocytes of non-pregnant women , women with threatened pre-term delivery , and men showed equivalent levels : 3 +\/- 1 , 3 +\/- 2 and 5 +\/- 4 fmol\/mg respectively . impaired UV-induced tyrosine phosphorylation Normal T lymphocytes whose surface expression of CD3 was depleted showed impaired UV-induced tyrosine phosphorylation and Ca2+ signals . impaired activation nf-kappab of the transcription factor T lymphocytes from patients with renal cell carcinoma ( RCC ) show reduced immune function and impaired activation of the transcription factor , NF-kappaB . kappa i b alpha In addition to the inducible phosphorylation after stimulation , B lymphocytes containing constitutive nuclear NF-kappa B revealed constitutively phosphorylated p65 and I kappa B alpha . little basal activity low nuclear expression Cloned , normal T lymphocytes show very little , if any , basal activity of the HIV enhancer and low nuclear expression of NF-kappa B , a potent transcriptional activator of the HIV enhancer . little basal activity of the HIV enhancer a potent transcriptional activator of the HIV enhancer Cloned , normal T lymphocytes show very little , if any , basal activity of the HIV enhancer and low nuclear expression of NF-kappa B , a potent transcriptional activator of the HIV enhancer . little basal activity of the HIV enhancer of nf-kappa b Cloned , normal T lymphocytes show very little , if any , basal activity of the HIV enhancer and low nuclear expression of NF-kappa B , a potent transcriptional activator of the HIV enhancer . phosphorylated p65 In addition to the inducible phosphorylation after stimulation , B lymphocytes containing constitutive nuclear NF-kappa B revealed constitutively phosphorylated p65 and I kappa B alpha . reduced immune function T lymphocytes from patients with renal cell carcinoma ( RCC ) show reduced immune function and impaired activation of the transcription factor , NF-kappaB . signals Normal T lymphocytes whose surface expression of CD3 was depleted showed impaired UV-induced tyrosine phosphorylation and Ca2+ signals . similar enhancement of Ig-secreting cells Lymphocytes from patients who have received anti-estrogen therapy show similar enhancement of Ig-secreting cells after PWM stimulation . 99 % suppression SLA-DQ antigen induction PIEC clones stably transfected with one of these constructs showed up to 99 % suppression of SLA-DR and SLA-DQ antigen induction and marked suppression of SLA-DRA mRNA induction . 99 % suppression marked suppression of SLA-DRA mRNA induction PIEC clones stably transfected with one of these constructs showed up to 99 % suppression of SLA-DR and SLA-DQ antigen induction and marked suppression of SLA-DRA mRNA induction . 99 % suppression of SLA-DR PIEC clones stably transfected with one of these constructs showed up to 99 % suppression of SLA-DR and SLA-DQ antigen induction and marked suppression of SLA-DRA mRNA induction . resistance In vitro , chronically HIV-infected cells of the lymphoid CEM line displayed resistance to glucocorticoid-induced apoptosis . activation IL-13 induces phosphorylation and activation of JAK2 Janus kinase in human colon carcinoma cell lines : similarities between IL-4 and IL-13 signaling . distinct STAT6-DNA binding complexes JAK3 Furthermore , we demonstrate that IL-13 , like IL-4 , induces distinct STAT6-DNA binding complexes and tyrosine phosphorylation of STAT6 and Janus kinase 3 ( JAK3 ) in NK and T cells . distinct STAT6-DNA binding complexes Janus kinase 3 Furthermore , we demonstrate that IL-13 , like IL-4 , induces distinct STAT6-DNA binding complexes and tyrosine phosphorylation of STAT6 and Janus kinase 3 ( JAK3 ) in NK and T cells . distinct STAT6-DNA binding complexes of STAT6 Furthermore , we demonstrate that IL-13 , like IL-4 , induces distinct STAT6-DNA binding complexes and tyrosine phosphorylation of STAT6 and Janus kinase 3 ( JAK3 ) in NK and T cells . dose IL-4 and IL-13 induced dose- and time-dependent increases in IL-1RI and IL-1RII mRNA levels . expression of a distinct subset of genes The Th2-type cytokines , interleukin-4 ( IL-4 ) and interleukin-13 ( IL-13 ) , induce expression of a distinct subset of genes in human monocytes , including FcepsilonRIIb ( CD23 ) , 15-lipoxygenase , IL-1 receptor antagonist ( IL-1ra ) , and type I and type II IL-1 receptors ( IL-1R ) . expression of a distinct subset of genes The Th2-type cytokines IL-4 and IL-13 induce expression of a distinct subset of genes in human monocytes . low levels of IFN-gamma secretion We demonstrate that , in primary NK cells , IL-13 , but not IL-4 , may induce low levels of IFN-gamma secretion . phosphorylation STAT6 Both IL-13 and IL-4 induced phosphorylation of IL-4 STAT ( STAT6 ) but not STAT1 , STAT3 , or STAT5 . phosphorylation of IL-4 STAT Both IL-13 and IL-4 induced phosphorylation of IL-4 STAT ( STAT6 ) but not STAT1 , STAT3 , or STAT5 . phosphorylation of JAK2 Janus kinase IL-13 induces phosphorylation and activation of JAK2 Janus kinase in human colon carcinoma cell lines : similarities between IL-4 and IL-13 signaling . rapid phosphorylation of four members of the known Janus family JAKs IL-13 caused rapid phosphorylation of the three out of four members of the known Janus family of kinases ( JAKs ) . rapid phosphorylation of four members of the known Janus family of kinases IL-13 caused rapid phosphorylation of the three out of four members of the known Janus family of kinases ( JAKs ) . the 12-lipoxygenase activity of murine macrophages The data presented here indicate that ( 1 ) the 12-lipoxygenase activity of murine macrophages is upregulated in vitro and in vivo by IL-4 and\/or IL-13 , ( 2 ) this upregulation requires expression of the transcription factor STAT6 , and ( 3 ) the constitutive expression of the enzyme appears to be STAT6 independent . the expression of genomic HIV mRNA IL-4 and IL-13 up-regulated the expression of both genomic and spliced HIV mRNA in monocytes cultured on Teflon , as determined by Northern analysis and p24 Ag assay . the expression of spliced HIV mRNA IL-4 and IL-13 up-regulated the expression of both genomic and spliced HIV mRNA in monocytes cultured on Teflon , as determined by Northern analysis and p24 Ag assay . the same complexes IL-13 Induced the same complexes as IL-4 , a finding explained by our studies implicating IL-4R as a shared component of the receptors . time-dependent increases IL-4 and IL-13 induced dose- and time-dependent increases in IL-1RI and IL-1RII mRNA levels . tyrosine phosphorylation Furthermore , we demonstrate that IL-13 , like IL-4 , induces distinct STAT6-DNA binding complexes and tyrosine phosphorylation of STAT6 and Janus kinase 3 ( JAK3 ) in NK and T cells . upregulation of the murine macrophage 12\/15-lipoxygenase activity Interleukin-4 and -13 induce upregulation of the murine macrophage 12\/15-lipoxygenase activity : evidence for the involvement of transcription factor STAT6 . the GATA-3 protein During the differentiation of naive CD4(+) T cells isolated from T cell receptor transgenic mice , GATA-3 gene expression was up-regulated in developing Th2 cells , but was down-regulated in Th1 cells , and antigen- or cAMP-activated Th2 cells ( but not Th1 cells ) expressed the GATA-3 protein . heterocomplexes STAT1 and STAT2 or STAT1 and STAT3 translated in reticulocyte lysate spontaneously form heterocomplexes when the translation lysates are mixed at 0 degrees C . rapamycin-resistant components Our present results show that IL-2- and PI 3-kinase-induced pathways for the regulation of E2F transcriptional activity include both rapamycin-resistant and rapamycin-sensitive components . rapamycin-sensitive components Our present results show that IL-2- and PI 3-kinase-induced pathways for the regulation of E2F transcriptional activity include both rapamycin-resistant and rapamycin-sensitive components . AP-1 kappa B dna binding TNF-alpha , IL-1 beta and phorbol myristate acetate ( PMA ) treatment increased AP-1 and NF kappa B DNA binding by up to 200 % but decreased CREB binding ( 38 % ) over a 60-min time course . NF kappa B dna binding TNF-alpha , IL-1 beta and phorbol myristate acetate ( PMA ) treatment increased AP-1 and NF kappa B DNA binding by up to 200 % but decreased CREB binding ( 38 % ) over a 60-min time course . PMA-dependent IL-5 production EL-4 cells also produce low levels of IL-5 when stimulated by PMA alone ; however , cAMP greatly augments PMA-dependent IL-5 production . a down-regulation of the levels of this proto-oncogene Nevertheless , dibutyryl cAMP induced a down-regulation of the levels of this proto-oncogene . activation In murine Ba\/F3 cells transfected with the human G-CSFR and NFS-60 cells constitutively expressing the murine G-CSFR , G-CSF induced tyrosine phosphorylation and activation of Jak1 , Jak2 , and Tyk2 . prominent tyrosine phosphorylation of a protein of a relative molecular mass of 80 kDa Antiphosphotyrosine immunoblots of whole cell lysates prepared from neutrophils show that the G-CSF rapidly induces prominent tyrosine phosphorylation of a protein of a relative molecular mass of 80 kDa . tyrosine phosphorylation Jak2 In murine Ba\/F3 cells transfected with the human G-CSFR and NFS-60 cells constitutively expressing the murine G-CSFR , G-CSF induced tyrosine phosphorylation and activation of Jak1 , Jak2 , and Tyk2 . tyrosine phosphorylation Tyk2 In murine Ba\/F3 cells transfected with the human G-CSFR and NFS-60 cells constitutively expressing the murine G-CSFR , G-CSF induced tyrosine phosphorylation and activation of Jak1 , Jak2 , and Tyk2 . tyrosine phosphorylation of Jak1 In murine Ba\/F3 cells transfected with the human G-CSFR and NFS-60 cells constitutively expressing the murine G-CSFR , G-CSF induced tyrosine phosphorylation and activation of Jak1 , Jak2 , and Tyk2 . mRNA expression of an immediate early gene c-fos Histamine induced mRNA expression of an immediate early gene c-fos . latent infection Human immunodeficiency virus ( HIV ) often causes latent infection . NF kappaB activation In Jurkat cells , a human T-cell lymphoma cell line , tumor necrosis factor-alpha ( TNF-alpha ) induces NF kappaB activation that is inhibited by PDTC . the accumulation of class II-CLIP complexes Expression of HLA-DO in a class II+ and DM+ , DO- human T cell line caused the accumulation of class II-CLIP complexes , indicating that HLA-DO blocked DM function in vivo and suggesting that HLA-DO is an important modulator of class II-restricted antigen processing . CD11b IL-4 enhanced CD11b , but inhibited CD26 expression and delayed CD13 loss . Cepsilon germline transcripts IL-4 induces Cepsilon germline transcripts and IgE isotype switching in B cells from patients with gammac chain deficiency . Germ line C transcripts Germ line C transcripts can be induced by IL-4 in the human B cell line , BL-2 . IgE isotype switching IL-4 induces Cepsilon germline transcripts and IgE isotype switching in B cells from patients with gammac chain deficiency . STAT-6 Electrophoretic mobility shift assays showed that p50\/p65\/c-Rel and STAT-6 are effectively induced by CD40L and IL-4 , respectively , and bind to specific DNA motifs within the ECS . Stat6 DNA binding activity IL-4 also induced Stat6 DNA binding activity from lysates of 1D4 but not E1C3 cells utilizing a radiolabeled immunoglobulin heavy chain germline epsilon promotor sequence ( Iepsilon ) in an electrophoretic mobility shift assay . TGF-beta1 mRNA IL-3 , IL-4 , and IL-5 independently up-regulated TGF-beta1 mRNA and product expression by eosinophils in all donors . a binding activity of BL-2 cells Utilizing a IFN-gamma activation site-like DNA sequence element located upstream of the I epsilon exon , we demonstrated by gel mobility shift assays that IL-4 induced a binding activity in the cytosol and nucleus of BL-2 cells . a multimerized response element We show that , whereas a multimerized response element from the germline IgE promoter was highly induced by IL-4 in Stat6-expressing Jurkat cells , the intact human IL-4 promoter was repressed under similar conditions . a weak up-regulation of VDR expression Treatment of B lymphocytes with the cytokine IL-4 ( IL-4 ) , in the absence of prior activation , induces a weak up-regulation of VDR expression but fails to generate vitamin D-responsive element ( VDRE ) -reactive nuclear protein complexes or to initiate the genomic transcription of 25-hydroxyvitamin D3 24-hydroxylase . activation PI3-kinase Both IL-4 and anti-CD40 mAb induced activation of phosphatidylinositol 3-kinase ( PI3-kinase ) , translocation of a zeta isoform of protein kinase C , and nuclear expression of NF-kappa B . activation of phosphatidylinositol 3-kinase Both IL-4 and anti-CD40 mAb induced activation of phosphatidylinositol 3-kinase ( PI3-kinase ) , translocation of a zeta isoform of protein kinase C , and nuclear expression of NF-kappa B . different C epsilon GAS DNA-protein binding complexes In contrast , IL-4 induces different C epsilon GAS DNA-protein binding complexes in both T and NK cells . dose IL-4 and IL-13 induced dose- and time-dependent increases in IL-1RI and IL-1RII mRNA levels . expression of a distinct subset of genes The Th2-type cytokines IL-4 and IL-13 induce expression of a distinct subset of genes in human monocytes . expression of gene IL-4 The molecular mechanisms by which IL-4 induces expression of the IL-4 gene are not known , although the IL-4-activated transcription factor signal transducer and activator of transcription 6 ( Stat6 ) is required for this effect . mRNA degradation Further examination reveals that , unlike IL-10 , IL-4 enhances mRNA degradation and does not suppress cytokine gene transcription . nuclear expression of nf-kappa b Both IL-4 and anti-CD40 mAb induced activation of phosphatidylinositol 3-kinase ( PI3-kinase ) , translocation of a zeta isoform of protein kinase C , and nuclear expression of NF-kappa B . p50\/p65\/c-Rel Electrophoretic mobility shift assays showed that p50\/p65\/c-Rel and STAT-6 are effectively induced by CD40L and IL-4 , respectively , and bind to specific DNA motifs within the ECS . phosphorylation STAT6 Both IL-13 and IL-4 induced phosphorylation of IL-4 STAT ( STAT6 ) but not STAT1 , STAT3 , or STAT5 . phosphorylation of IL-4 STAT Both IL-13 and IL-4 induced phosphorylation of IL-4 STAT ( STAT6 ) but not STAT1 , STAT3 , or STAT5 . product expression IL-3 , IL-4 , and IL-5 independently up-regulated TGF-beta1 mRNA and product expression by eosinophils in all donors . robust Janus 3 JAK3 kinase activity Congruous with the involvement of a Stat protein , IL-4 induced robust Janus kinase 3 ( JAK3 ) activity in BL-2 cells . the 12-lipoxygenase activity of murine macrophages The data presented here indicate that ( 1 ) the 12-lipoxygenase activity of murine macrophages is upregulated in vitro and in vivo by IL-4 and\/or IL-13 , ( 2 ) this upregulation requires expression of the transcription factor STAT6 , and ( 3 ) the constitutive expression of the enzyme appears to be STAT6 independent . the expression of genomic HIV mRNA IL-4 and IL-13 up-regulated the expression of both genomic and spliced HIV mRNA in monocytes cultured on Teflon , as determined by Northern analysis and p24 Ag assay . the expression of spliced HIV mRNA IL-4 and IL-13 up-regulated the expression of both genomic and spliced HIV mRNA in monocytes cultured on Teflon , as determined by Northern analysis and p24 Ag assay . time-dependent increases IL-4 and IL-13 induced dose- and time-dependent increases in IL-1RI and IL-1RII mRNA levels . translocation of a zeta isoform of protein kinase c Both IL-4 and anti-CD40 mAb induced activation of phosphatidylinositol 3-kinase ( PI3-kinase ) , translocation of a zeta isoform of protein kinase C , and nuclear expression of NF-kappa B . I kappa B-alpha mRNA Subsequently , I kappa B-alpha mRNA and protein levels are quickly induced by the activated NF-kappa B . protein levels Subsequently , I kappa B-alpha mRNA and protein levels are quickly induced by the activated NF-kappa B . the I kappa B-alpha mRNA Transfection studies reveal that the I kappa B-alpha mRNA and the encoded protein are potently induced by NF-kappa B and by homodimers of p65 and of c-Rel . the encoded protein Transfection studies reveal that the I kappa B-alpha mRNA and the encoded protein are potently induced by NF-kappa B and by homodimers of p65 and of c-Rel . retinaldehyde dehydrogenase 2 expression TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3 . the formation of the IFN-gamma-induced complex The IL-4-induced complex reacted with anti-STAT ( signal transducers and activators of transcription ) 6 , resulting in a supershift whereas the formation of the IFN-gamma-induced complex was inhibited by anti-STAT 1 . the EPO signal In contrast , the addition of GM-CSF to the M-TAT\/EPO cell culture decreased the amount of hemoglobin , even in the presence of EPO , indicating that the EPO signal for erythroid differentiation is suppressed by GM-CSF . NF kappaB NO derived from nNOS in glia inhibits the transcription factor nuclear factor kappaB ( NF kappaB ) as NOS inhibitors enhance basal NF kappaB activation . cytokine-induced endothelial cell activation We find that iNO produced by murine macrophage-like cells , RAW264.7 , can inhibit cytokine-induced endothelial cell activation in a separated and mixed endothelial-RAW264.7 coculture system . interleukin IL -1 alpha-stimulated VCAM-1 expression In a concentration-dependent manner , NO inhibited interleukin ( IL ) -1 alpha-stimulated VCAM-1 expression by 35-55 % as determined by cell surface enzyme immunoassays and flow cytometry . the activation of b nuclear factor-kappa Immunofluorescence studies using an Ab to the RelA ( p65 ) subunit of nuclear factor-kappa B revealed that iNO inhibited the activation of nuclear factor-kappa B . the transcription factor nuclear factor kappaB NO derived from nNOS in glia inhibits the transcription factor nuclear factor kappaB ( NF kappaB ) as NOS inhibitors enhance basal NF kappaB activation . neutrophil development These results show that PEBP2betaMYH11 can impair neutrophil development and provide evidence that alterations of Pebp2 can contribute to the genesis of myelodysplasia . neutrophilic differentiation In addition , PEBP2betaMYH11 inhibited neutrophilic differentiation in colonies derived from hematopoietic progenitors . LPS induction of collagenase transcription 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 . The expression of gene QR The expression of the QR gene is regulated by the transcription factor AP-1 . Transcriptional induction of collagenase-1 Transcriptional induction of collagenase-1 in differentiated monocyte-like ( U937 ) cells is regulated by AP-1 and an upstream C\/EBP-beta site . IL-2 receptor alpha gene transcription We have shown that interleukin-1 ( IL-1 ) and IL-2 control IL-2 receptor alpha ( IL-2R alpha ) gene transcription in CD4-CD8- murine T lymphocyte precursors . IL-2R alpha gene transcription We have shown that interleukin-1 ( IL-1 ) and IL-2 control IL-2 receptor alpha ( IL-2R alpha ) gene transcription in CD4-CD8- murine T lymphocyte precursors . Transcriptional control of the IL-5 gene IL-5 synthesis Transcriptional control of the IL-5 gene by human helper T cells : IL-5 synthesis is regulated independently from IL-2 or IL-4 synthesis . the cellular distribution of Aiolos Indirect immunofluorescence shows that IL-2 controls the cellular distribution of Aiolos and induces its tyrosine phosphorylation , required for dissociation from Ras . transcription Interleukin-1 and interleukin-2 control transcription via distinct cis-acting elements . transcription of gene different The exact mechanism by which IL-2 regulates transcription of different genes is presently unknown . IL-4R p140 In addition , IL-13 phosphorylated insulin response substrate-1 , IL-4R p140 , JAK1 , and Tyk2 , but not JAK3 kinase . JAK1 In addition , IL-13 phosphorylated insulin response substrate-1 , IL-4R p140 , JAK1 , and Tyk2 , but not JAK3 kinase . Tyk2 In addition , IL-13 phosphorylated insulin response substrate-1 , IL-4R p140 , JAK1 , and Tyk2 , but not JAK3 kinase . insulin response substrate-1 In addition , IL-13 phosphorylated insulin response substrate-1 , IL-4R p140 , JAK1 , and Tyk2 , but not JAK3 kinase . a critical role The cytokines interleukin ( IL ) -4 and IL-13 play a critical role in inducing Cepsilon germline transcripts and IgE isotype switching in human B cells . a crucial role Interleukin-12 ( IL-12 ) , a heterodimeric cytokine produced by activated monocytes and dendritic cells , plays a crucial role in regulating interferon ( IFN ) -gamma production and in the generation of IFN-gamma-producing T helper 1 ( Th1 ) cells . a prominent role This pro-inflammatory cytokine plays a prominent role in the development of Th1 cell-mediated immune responses . IL-2 deprivation apoptosis We found that IL-2 , interferon-alpha ( IFN-alpha ) , and IFN-beta inhibited IL-2 deprivation apoptosis in Th0 , Th1 , and Th2 clones . the DEX-mediated IkappaBalpha induction Interestingly , the DEX-mediated IkappaBalpha induction was completely inhibited by IL-2 , but not IL-4 , in Th1 cells , while the reverse profile was seen in Th2 cells . the functional synergy A specific inhibitor of p38 MAP kinase completely inhibits the serine phosphorylation of STAT1 and STAT3 induced by IL-12 and IL-2 and abrogates the functional synergy between IL-12 and IL-2 without affecting STAT tyrosine phosphorylation . this induction of cell death We previously reported that dexamethasone ( DEX ) , a synthetic glucocorticoid , causes apoptosis in mature Th cell lines , and that this induction of cell death is prevented by specific cytokines , namely , by IL-2 in Th1 cells and by IL-4 in Th2 cells . a pertinent model Cytokines control growth , differentiation , death , and function of cells of lymphocytic , hemopoietic systems , and together with nerve cells provide a pertinent model to study intercellular communications and intercellular signal networks . the expression level of the SRG3 protein The expression of anti-sense RNA to SRG3 mRNA in a thymoma cell line , S49.1 , reduced the expression level of the SRG3 protein , and decreased the apoptotic cell death induced by glucocorticoids . LPS induction of collagenase transcription 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 . The expression of gene QR The expression of the QR gene is regulated by the transcription factor AP-1 . Transcriptional induction of collagenase-1 Transcriptional induction of collagenase-1 in differentiated monocyte-like ( U937 ) cells is regulated by AP-1 and an upstream C\/EBP-beta site . IFN alpha production As glucocorticoids regulate interferon-alpha ( IFN alpha ) production , we hypothesized that IFN alpha , a cytokine produced predominantly by monocytes in AIDS , should be increased in cortisol-resistant AIDS , attributing the lack of cortisol inhibition to IFN alpha production . IL-10 secretion We conclude that glucocorticoids differentially modulate TNFalpha and IL-10 secretion by human monocytes in a LPS dose-dependent fashion and that the sensitivity of these cells to glucocorticoids is altered by TNFalpha or IL-10 pretreatment ; TNFalpha blocks their effects , whereas IL-10 acts synergistically with glucocorticoids . TNFalpha secretion We conclude that glucocorticoids differentially modulate TNFalpha and IL-10 secretion by human monocytes in a LPS dose-dependent fashion and that the sensitivity of these cells to glucocorticoids is altered by TNFalpha or IL-10 pretreatment ; TNFalpha blocks their effects , whereas IL-10 acts synergistically with glucocorticoids . effects Glucocorticoids are mediating their effects after binding to an intracellular receptor belonging to the steroid receptor superfamily : the glucocorticoid receptor ( GR ) . interferon-alpha production As glucocorticoids regulate interferon-alpha ( IFN alpha ) production , we hypothesized that IFN alpha , a cytokine produced predominantly by monocytes in AIDS , should be increased in cortisol-resistant AIDS , attributing the lack of cortisol inhibition to IFN alpha production . the expression of CD11\/CD18 integrins The aim of the present study was to investigate whether glucocorticoids also regulate the expression of L-selectin and CD11\/CD18 integrins on human neutrophil granulocytes . the expression of L-selectin integrins The aim of the present study was to investigate whether glucocorticoids also regulate the expression of L-selectin and CD11\/CD18 integrins on human neutrophil granulocytes . suppressive effects However , suppression of IL-1R gene expression by IFN-gamma and IL-10 was associated with decreased tyrosine phosphorylation and nuclear translocation of the IL-4\/IL-13-inducible transcription factor , Stat6 , suggesting a potential mechanism by which IFN-gamma and IL-10 may mediate their suppressive effects . the expression of several cytokines Interferon-gamma ( IFN-gamma ) modulates the expression of several cytokines by human monocytes at the transcriptional level . IFNalpha-induced gene expression Because monocytes and macrophages are important mediators of Th1-type responses , such as delayed-type hypersensitivity , we sought to determine if IL-10 could directly mediate inhibition of IFNgamma- and IFNalpha-induced gene expression in these cells . inhibition of IFNgamma Because monocytes and macrophages are important mediators of Th1-type responses , such as delayed-type hypersensitivity , we sought to determine if IL-10 could directly mediate inhibition of IFNgamma- and IFNalpha-induced gene expression in these cells . suppressive effects However , suppression of IL-1R gene expression by IFN-gamma and IL-10 was associated with decreased tyrosine phosphorylation and nuclear translocation of the IL-4\/IL-13-inducible transcription factor , Stat6 , suggesting a potential mechanism by which IFN-gamma and IL-10 may mediate their suppressive effects . the production of different cytokines These results indicate that LTB4 may regulate the production of different cytokines by modulating the yield and\/or the function of transcription factors such as AP-1-binding proto-oncogene products . transactivation of a heterologous promoter construct In addition , LTB4 mediated transactivation of a heterologous promoter construct containing the NF-chi B or the NF-IL6 enhancer , but not the AP-1 enhancer . binding of the immune complex Fab fragment of anti-E. chaffeensis immunoglobulin G complexed with E. chaffeensis did not induce any of these three cytokines , indicating that ehrlichial binding is required for IL-1beta mRNA expression and that binding of the immune complex to the Fc gamma receptor is required for TNF-alpha and IL-6 mRNA expression and enhanced IL-1beta mRNA expression . a decrease Jurkat T cells pretreated with NH2Cl ( 20-70 microM ) showed a decrease in the expression of the interleukin-2 receptor alpha chain following PMA stimulation . a characteristic competitive binding profile The binding sites fulfil the required criteria for specific steroid binding sites however differ somewhat from the classic androgen receptors from genital skin fibroblast : in fertile adult males ( n = 20 ) the binding sites showed ( 1 ) a high affinity for testosterone ( 1.32 +\/- 0.49 nM ; mean +\/- SD ) , ( 2 ) a saturable capacity ( 184 +\/- 52 binding sites per cell ; mean +\/- SD ) , and ( 3 ) a characteristic competitive binding profile for other steroid hormones ( relative binding affinities : testosterone = dihydrotestosterone > 17 beta-estradiol > progesterone , whereas aldosterone , 17-hydroxy-progesterone and cortisol did not compete appreciably ) . a high affinity The binding sites fulfil the required criteria for specific steroid binding sites however differ somewhat from the classic androgen receptors from genital skin fibroblast : in fertile adult males ( n = 20 ) the binding sites showed ( 1 ) a high affinity for testosterone ( 1.32 +\/- 0.49 nM ; mean +\/- SD ) , ( 2 ) a saturable capacity ( 184 +\/- 52 binding sites per cell ; mean +\/- SD ) , and ( 3 ) a characteristic competitive binding profile for other steroid hormones ( relative binding affinities : testosterone = dihydrotestosterone > 17 beta-estradiol > progesterone , whereas aldosterone , 17-hydroxy-progesterone and cortisol did not compete appreciably ) . a saturable capacity The binding sites fulfil the required criteria for specific steroid binding sites however differ somewhat from the classic androgen receptors from genital skin fibroblast : in fertile adult males ( n = 20 ) the binding sites showed ( 1 ) a high affinity for testosterone ( 1.32 +\/- 0.49 nM ; mean +\/- SD ) , ( 2 ) a saturable capacity ( 184 +\/- 52 binding sites per cell ; mean +\/- SD ) , and ( 3 ) a characteristic competitive binding profile for other steroid hormones ( relative binding affinities : testosterone = dihydrotestosterone > 17 beta-estradiol > progesterone , whereas aldosterone , 17-hydroxy-progesterone and cortisol did not compete appreciably ) . activity In EBV-transformed B clones , the chi B site exerted the strongest inducible activity ; the NF-AT binding sites showed either no or only weak activity compared to Jurkat T cells . little conservation Binding sites at the core region show little conservation with consensus sites . some sequence similarity Because the binding site showed some sequence similarity with the nuclear factor of activated T cells ( NFAT ) binding site , we compared the kinetics of induction of the two binding complexes and the molecular masses of the two proteins . an altered B-cell maturation pattern In fact , transgenic bone marrow cells cocultured with a bone marrow-derived stromal cell line revealed an altered B-cell maturation pattern . a conserved C-terminal domain The cDNA encoding hTAFII105 reveals a highly conserved C-terminal domain shared by hTAFII130 and oTAFII110 , while the N-terminal coactivator domain has diverged significantly . a moderate correlation While controls showed a moderate correlation between binding affinity of the GR in lymphocytes and regulatory function at the hypothalamic level , the patients did not . the same differentiation response Furthermore , HL-60 cells transduced with a bcl-2 expression vector showed the same differentiation response to retinoids as did parental HL-60 cells even though apoptosis was inhibited in these bcl-2-transduced cells , suggesting that differentiation and apoptosis are regulated independently in myeloid leukemic cells . translocation of PKC activity Although HL-60 and HL-60\/vinc\/R cells demonstrated translocation of PKC activity , this subcellular redistribution was undetectable in HL-60\/vinc cells . any effect Furthermore , neither IL-10 nor IL-4 showed any effect on I-kappa B mRNA expression as determined by Northern experiments . little inhibitory effect IL-4 , another cytokine that inhibits cytokine mRNA accumulation in monocytes , shows little inhibitory effect on LPS-induced NF kappa B activation . a decrease of a 47-kDa protein The NH2Cl-treated neutrophils showed a decrease in both PKC activity and PMA-induced phosphorylation of a 47-kDa protein , which corresponds to the cytosolic factor of NADPH oxidase , p47 ( phox ) . a marked decrease Neutrophils pretreated with NH2Cl ( 30-50 microM ) showed a marked decrease in the respiratory burst activity induced by phorbol 12-myristate 13-acetate ( PMA ) , which is a potent PKC activator . IL-10 AIDS-C patients showed low IL-2 and high IL-4 , IL-10 , and IgE concentratios ; conversely , AIDS-GR patients showed high IL-2 and low IL-4 and IgE concentrations . IgE concentrations AIDS-C patients showed low IL-2 and high IL-4 , IL-10 , and IgE concentratios ; conversely , AIDS-GR patients showed high IL-2 and low IL-4 and IgE concentrations . IgE concentratios AIDS-C patients showed low IL-2 and high IL-4 , IL-10 , and IgE concentratios ; conversely , AIDS-GR patients showed high IL-2 and low IL-4 and IgE concentrations . a morning-to-afternoon decline RESULTS : Both the patients and the normal comparison subjects showed a morning-to-afternoon decline in glucocorticoid receptor concentrations , paralleling the normal diurnal decline in cortisol levels . an improvement All asthmatic patients showed an improvement in their FEV1 values after corticosteroid treatment ( per cent of predicted value 68.28 +\/- 4.93 versus 95.57 +\/- 6.41 , P < 0.02 ) , and a significant decrease for glucocorticoid receptor mRNA expression ( P < 0.02 ) was observed in their monocytes . elevated antibody titers While the sera of EBV-negative individuals ( 0\/3 ) or healthy carriers ( 0\/33 ) did not contain detectable levels of antibodies , patients with mononucleosis ( 5\/18 ) , chronic EBV infection ( 2\/7 ) , EBV reactivation ( 7\/20 ) and human immunodeficiency virus infection ( 5\/24 ) showed elevated antibody titres against the enzyme . elevated circulating levels of cortisol Patients with HIV infections often show elevated circulating levels of cortisol , suggesting some misfunction in the regulatory systems that maintain the levels of this critical hormone . high IL-2 AIDS-C patients showed low IL-2 and high IL-4 , IL-10 , and IgE concentratios ; conversely , AIDS-GR patients showed high IL-2 and low IL-4 and IgE concentrations . high IL-4 AIDS-C patients showed low IL-2 and high IL-4 , IL-10 , and IgE concentratios ; conversely , AIDS-GR patients showed high IL-2 and low IL-4 and IgE concentrations . higher NF-kappaB binding activity Patients with diabetic nephropathy showed higher NF-kappaB binding activity in Electrophoretic Mobility Shift Assays and stronger immunohistological staining for activated NF-kappaBp65 than patients without renal complications . insufficient suppression of serum cortisol concentrations All patients showed insufficient suppression of serum cortisol concentrations in the overnight 1-mg dexamethasone test . low IL-2 AIDS-C patients showed low IL-2 and high IL-4 , IL-10 , and IgE concentratios ; conversely , AIDS-GR patients showed high IL-2 and low IL-4 and IgE concentrations . low IL-4 AIDS-C patients showed low IL-2 and high IL-4 , IL-10 , and IgE concentratios ; conversely , AIDS-GR patients showed high IL-2 and low IL-4 and IgE concentrations . lower concentration Patients without phosphate supplementation showed significantly lower concentration ( 21.7 +\/- 5.1 fmol\/mg protein , mean +\/- SEM ) compared to the normal controls ( 60.7 +\/- 4.0 ) . monoclonal PMNCs All three RARS patients showed monoclonal PMNCs . no hypergammaglobulinemia Stronger c-myc mRNA expression was detected in labial salivary glands of patients with longer disease duration ( p less than or equal to 0.002 ) and more intense T lymphocyte infiltrates ( p less than 0.05 ) although these patients revealed no hypergammaglobulinemia . no significant improvements The resistant patients showed no significant improvements in airflow limitation . partial resistance Lymphocytes of patients with rheumatoid arthritis ( RA ) have diminished receptor density ; thus , patients with RA should show partial resistance to glucocorticoids . a pronounced deficiency Peripheral blood lymphocytes ( PBL ) and alloreactive T cell lines of two male infants born to consanguinous parents and presenting with severe combined immunodeficiency ( SCID ) showed a pronounced deficiency in T cell activation . Purified peripheral eosinophils METHODS : Purified peripheral eosinophils were stimulated with IFN-gamma at 37 degrees C for 1-60 min . CD40 responses G28-5 sFv was a more potent agonist than G28-5 IgG and was able to stimulate CD40 responses by B cells and monocytes . B-cell activation Cyclosporin A and FK506 inhibit T- and B-cell activation and other processes essential to an effective immune response . CD95L transcription Our data also show that the immunosuppressive agent cyclosporin A down-regulates CD95L transcription by inhibiting the function of this positive regulatory element G0S2 Cyclosporin A inhibits early mRNA expression of G0\/G1 switch gene 2 ( G0S2 ) in cultured human blood mononuclear cells . IL-2 gene transcription We asked whether dexamethasone ( Dex ) and cyclosporin A ( CsA ) inhibit IL-2 gene transcription by interfering with the activity of nuclear proteins that bind to the IL-2 promoter . Inducible nuclear factor binding Inducible nuclear factor binding to the kappa B elements of the human immunodeficiency virus enhancer in T cells can be blocked by cyclosporin A in a signal-dependent manner . NFAT activation With these clones , we demonstrated that NFAT activation induced by phorbol 12-myristate 13-acetate and ionomycin was inhibited by both cyclosporin A ( CsA ) ( IC50 = 8 nM ) and FK506 ( IC50 = 160 pM ) , presumably by inhibition of calcineurin activity . Oct-2 mRNA induction Oct-2 mRNA induction during antigen-driven T-cell activation was blocked by cyclosporin A , as well as by protein synthesis inhibitors . T Cyclosporin A and FK506 inhibit T- and B-cell activation and other processes essential to an effective immune response . The activation The activation by p59fyn plus PMA was blocked by EGTA and by the immunosuppressant drug cyclosporin A . The activation of calcineurin of NF-ATc The activation of calcineurin and the nuclear import of NF-ATc can both be blocked by cyclosporin A or FK506 in complex with their respective immunophilins . The activation the nuclear import of NF-ATc The activation of calcineurin and the nuclear import of NF-ATc can both be blocked by cyclosporin A or FK506 in complex with their respective immunophilins . The appearance of the CMAT binding complex The appearance of the CMAT binding complex was inhibited by both cyclosporin A and rapamycin . The shift 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 . a calcium-dependent signal The immunosuppressant drug cyclosporin A blocks a calcium-dependent signal from the T-cell receptor ( TCR ) that normally leads to T-cell activation . early events Cyclosporin A impaired not only early and late , but also immediate events ; however , addition of TNF-alpha prevented all inhibition . early mRNA expression of gene G0\/G1 switch 2 Cyclosporin A inhibits early mRNA expression of G0\/G1 switch gene 2 ( G0S2 ) in cultured human blood mononuclear cells . expression of egr-2 As with egr-3 , expression of egr-2 was blocked by cyclosporin A . expression of gene Few known genes ( IL-2 , members of the IL-8 family , interferon-gamma ) are induced in T cells only through the combined effect of phorbol myristic acetate ( PMA ) and a Ca(2+)-ionophore , and expression of only these genes can be fully suppressed by Cyclosporin A ( CyA ) . function When expressed in Jurkat T cells , recombinant NFAT1 is regulated , as expected , by the calmodulin-dependent phosphatase calcineurin , and its function is inhibited by the immunosuppressive agent cyclosporin A ( CsA ) . immediate events Cyclosporin A impaired not only early and late , but also immediate events ; however , addition of TNF-alpha prevented all inhibition . inhibiting Our data also show that the immunosuppressive agent cyclosporin A down-regulates CD95L transcription by inhibiting the function of this positive regulatory element it While the activation of the IL-2 promoter and an NFAT-driven minimal promoter by Tpl-2 was fully blocked by the dominant negative mutant NFAT delta418 , it was only partially blocked by the calcineurin inhibitor cyclosporin A suggesting that the Tpl-2-mediated NFAT activation is under the control of a combination of calcineurin-dependent and independent pathways . late events Cyclosporin A impaired not only early and late , but also immediate events ; however , addition of TNF-alpha prevented all inhibition . monocyte tissue factor activation Cyclosporin A inhibits monocyte tissue factor activation in cardiac transplant recipients . other processes essential Cyclosporin A and FK506 inhibit T- and B-cell activation and other processes essential to an effective immune response . the activation-induced changes of phosphoproteins Finally , the activation-induced changes in one set of phosphoproteins were dramatically inhibited by cyclosporin A . the induction of NF-MATp35 Similar to its effect on IL-2 production , cyclosporin A inhibited the induction of NF-MATp35 . the production of IL-2 Cyclosporin A ( CsA ) and FK506 inhibit the production of IL-2 in T lymphocytes at the level of gene transcription . the synergistic activation of JNK Similar to its effect on IL-2 induction , cyclosporin A ( CsA ) inhibited the synergistic activation of JNK , and a competitive inhibitor of Jun phosphorylation by JNK inhibited IL-2 promoter activation . the synergistic induction of IL-8 expression Furthermore , cyclosporin A , but not rapamycin , blocked the synergistic induction of IL-8 expression achieved with anti-CD3 and anti-CD28 costimulation . transcription Using constructs in which mRNA production controlled by a specific transcription factor could be readily measured we found that both cyclosporin A and FK506 completely inhibited transcription activated by NF-AT , NFIL2 A , NFIL2 B and partially inhibited transcription activated by NF kappa B . transcriptional activation Cyclosporin A and FK506 inhibited only transcriptional activation that was dependent on Ca2+ mobilization . translocation of the cytoplasmic component FK506 and cyclosporin A block translocation of the cytoplasmic component without affecting synthesis of the nuclear subunit . PKC downstream events Nevertheless , forskolin also inhibits PKC downstream events , such as c-jun expression , which is critical for the activation process of T cells . TG PMA- but not TG-induced IL-2R alpha is inhibited by the PKC inhibitor H7 , whereas TG- but not PMA-induced IL-2R alpha was inhibited by cholera toxin , forskolin and 1,9-dideoxy forskolin . TNFalpha factor expression Both forskolin and dibutyryl cAMP , which elevate intracellular cAMP by independent mechanisms , inhibited TNFalpha and tissue factor expression at the level of transcription . anti-CD3-induced shift We found that the adenylate cyclase activator , forskolin , inhibits anti-CD3-induced shift in Lck electrophoretic mobility , suggesting an intervention at the TCR-coupled phosphoinositide turnover that precedes the activation of PKC . tissue factor expression Both forskolin and dibutyryl cAMP , which elevate intracellular cAMP by independent mechanisms , inhibited TNFalpha and tissue factor expression at the level of transcription .