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IL-2 Expression (il-2 + expression)
Selected AbstractsICER/CREM-mediated transcriptional attenuation of IL-2 and its role in suppression by regulatory T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2007Josef Bodor Dr. Abstract Here, we report that inducible cAMP early repressor/cAMP response element modulator (ICER/CREM) is induced early in CD25+CD4+ regulatory T cell (TR) assays mainly in activated Foxp3, effector T cells and this induction correlates with sharp decrease in number of IL-2-expressing T cells. Importantly, RNAi targeting of ICER/CREM in responder CD25,CD4+ T cells antagonizes TR -mediated suppression. Moreover, forced expression of Foxp3 in naive CD25, T cells induces constitutive expression of ICER/CREM in T cells with a regulatory phenotype. Foxp3 facilitates expression of ICER/CREM both in Foxp3 transductants as well as CD25, responder T cells suggesting that induction of TR function in suppression assays may utilize contact-dependent interaction. Indeed, CTLA-4 blockade or use of B7-deficient CD25, responder T cells prevents ICER/CREM accumulation and leads to the rescue of IL-2 expression. Therefore, we propose that CTLA-4 binding to B7 ligands expressed on activated ligand-bearing Foxp3, effector T cells results in ICER/CREM-mediated transcriptional attenuation of IL-2. Collectively, these data suggest that Foxp3 expression in TR cells imposes suppression in contact-dependent fashion by induction of constitutive ICER/CREM expression in activated CD25+ Foxp3, T cell effectors thus preventing them from producing IL-2. [source] Altered expression of cytokines and sex steroid receptors in the reproductive tract of cysticercotic male micePARASITE IMMUNOLOGY, Issue 2 2010M. RODRÍGUEZ-DORANTES Summary Infection with Taenia crassiceps cysticerci in male mice produces an increase in serum oestradiol levels, whereas serum testosterone is abolished. Concomitantly, complete atrophy of the reproductive tract of infected male mice is observed. The present study was undertaken to determine the expression pattern of cytokines involved in steroidogenesis and sex steroid receptors in the reproductive tissues of normal and infected male mice, and relating this expression pattern to whole parasite counts, serum sex steroid levels and pathology of the reproductive tract in infected male mice. The expression of IL-4, IFN-, and TNF-, in testes and seminal vesicles was markedly increased in infected mice; however, IL-10 and IL-1, expression was importantly decreased in the same organs. IL-2 expression in reproductive tissues was not affected by infection. The infection markedly induced the expression of androgen receptor, in both reproductive organs tested, while subtypes of oestrogen receptors were decreased in both tissues. [source] Reversing interleukin-2 inhibition mediated by anti,double-stranded DNA autoantibody ameliorates glomerulonephritis in MRL- lpr/lpr miceARTHRITIS & RHEUMATISM, Issue 8 2010Ying-Chyi Song Objective Our previous study demonstrated that anti,double-stranded DNA (anti-dsDNA) antibodies involved in lupus nephritis down-regulate the production of interleukin-2 (IL-2) in T cells, which in turn, contributes to the defective production of cytotoxic cells and to activation-induced cell death in vitro. To reveal novel molecular targets for lupus therapy, the molecular mechanisms of IL-2 down-regulation by anti-dsDNA were studied. Methods Anti-dsDNA monoclonal antibody (mAb) 9D7 was used to study the molecular mechanisms of IL-2 production in vitro. Treatment with arginine-rich peptide, a penetration inhibitor, was used to verify the effect of internalization of anti-dsDNA on the production of IL-2. The signaling pathway for IL-2 expression induced by anti-dsDNA was analyzed by using kinase inhibitors. The therapeutic effects of these inhibitors were evaluated in MRL- lpr/lpr mice. Results Inhibition of IL-2 production in activated Jurkat cells and human T cells pretreated with mAb 9D7 was reversed by treatment with the arginine-rich peptide. Levels of pAkt and phosphorylated glycogen synthase kinase 3 (pGSK-3) were reduced in activated Jurkat cells that had been pretreated with mAb 9D7. The inhibition of IL-2 production by mAb 9D7 was counteracted by pretreating the cells with LiCl (a GSK-3 inhibitor). However, IL-2 reduction was not recovered in the cells pretreated with ERK and JNK inhibitors. Furthermore, MRL- lpr/lpr mice injected with LiCl or with arginine-rich peptide restored the IL-2 production and reduced the manifestations of lupus. Conclusion These findings suggest that penetration of T cells by anti-dsDNA may inhibit IL-2 production by activating GSK-3. Moreover, blocking GSK-3 activation as well as inhibiting anti-dsDNA penetration is a potential therapeutic approach for lupus. [source] Activation of synoviolin promoter in rheumatoid synovial cells by a novel transcription complex of interleukin enhancer binding factor 3 and GA binding protein ,ARTHRITIS & RHEUMATISM, Issue 1 2009Toshihiko Izumi Objective Synoviolin is an E3 ubiquitin ligase, and its overexpression is implicated in the pathogenesis of rheumatoid arthritis (RA). We reported previously that Ets binding site 1 (EBS-1) within the synoviolin promoter is crucial for the expression of synoviolin, and GA binding protein (GABP) binds to this site. This study was undertaken to elucidate the precise mechanisms of transcriptional regulation via EBS-1. Methods We performed purification and identification of complex components that bind to EBS-1 and inspected their contributions to the transcriptional regulation of synoviolin in rheumatoid synovial cells. We biochemically purified proteins that had EBS-1 binding activity and identified the proteins using liquid chromatography tandem mass spectrometry analysis. The identified proteins were verified to recruit and form the complex on EBS-1 using electrophoretic mobility shift assay and coimmunoprecipitation assay. Furthermore, their transcription activities were tested by reporter assays and RNA interference experiments. Results We identified interleukin enhancer binding factor 3 (ILF-3) as a novel factor in the complex. ILF-3 was demonstrated to activate the synoviolin promoter via association with GABP, in rheumatoid synovial cells. In addition, further activation was observed with ILF-2 and GABP,, previously reported interactants of ILF-3 and GABP,, respectively. Moreover, ILF-3,knockdown experiments showed reduced expression of the synoviolin gene. Conclusion Our findings indicate that ILF-3, which has been known to regulate IL-2 expression in T cells, up-regulates synoviolin expression with GABP, in rheumatoid synovial cells. ILF-3 might be a target for RA treatment through its effect on IL-2 in T cells and synoviolin in rheumatoid synovial cells. [source] | ||||||||||