共查询到20条相似文献,搜索用时 31 毫秒
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Protein kinase A regulates GATA-3-dependent activation of IL-5 gene expression in Th2 cells 总被引:1,自引:0,他引:1
Klein-Hessling S Jha MK Santner-Nanan B Berberich-Siebelt F Baumruker T Schimpl A Serfling E 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(6):2956-2961
Treatment of Th cells with compounds that elevate cAMP levels augments Th2-type lymphokine expression, in particular the synthesis of IL-5. Using primary murine CD4(+) T lymphocytes, we show in this study that inhibition of protein kinase A (PKA) activity in Th2 effector cells impairs IL-5 synthesis, whereas the expression of PKA catalytic subunit alpha enhances IL-5 synthesis in Th0 cells. In addition, we observed by coexpression of PKA catalytic subunit and GATA-3 in Th1 cells that the stimulatory effect of PKA is dependent on GATA-3 activity. These data demonstrate that activation of PKA in Th effector cells induces the IL-5 gene expression in a GATA-3-dependent manner. 相似文献
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Kozuka T Sugita M Shetzline S Gewirtz AM Nakata Y 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(11):5974-5982
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Kishikawa H Sun J Choi A Miaw SC Ho IC 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(8):4414-4420
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Chen L Grabowski KA Xin JP Coleman J Huang Z Espiritu B Alkan S Xie HB Zhu Y White FA Clancy J Huang H 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(4):2059-2066
Innate effector cells that produce Th2-type cytokines are critical in Th2 cell-mediated immune responses. However, it is not known how these cells acquire the ability to produce Th2 cytokines. IL-4 is a potent inducer that directs differentiation of naive CD4(+) T cells into CD4(+) Th2 effector cells. To determine whether IL-4 can induce differentiation and expansion of Th2 cytokine-producing innate cells, we used mice whose il-4 gene was replaced by a knock-in green fluorescence protein (gfp) gene. We found that, directly ex vivo, IL-4 increased the number of GFP(+) cells in the airway and the lung tissue in an Ag-specific manner. The majority of GFP(+) cells were eosinophils, suggesting that IL-4 plays a pivotal role in expanding IL-4-producing eosinophils in vivo. IL-4-producing eosinophils showed some unique features compared with IL-4-producing CD4(+) T cells. They exhibited biallelic expression of the il-4 gene when stimulated and were more dominant IL-4- and IL-5-producing cells. Furthermore, we show that IL-4 drove bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils in vitro. These results strongly suggest IL-4 is a potent factor in directing bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils. 相似文献
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The development of Th subset is accompanied by subset-specific chromatin remodeling of cytokine gene loci. In this study, we show that the C-terminal, but not the N-terminal zinc finger (N-finger) of GATA-3 mediates the association with the IL-4/IL-13 intergenic DNase I hypersensitive site and the induction of an extended DNase I hypersensitivity on the IL-4/IL-13 locus. Consistently, deletion of the transactivation domains or the C-finger, but not the N-finger, abrogated the induction of IL-4 and IL-13 as well as the down-regulation of IFN-gamma. In contrast, the N-finger of GATA-3 was indispensable for the binding to the IL-5 promoter and the induction of IL-5. The selective use of the N-finger may underlie the differential roles of GATA-3 in the induction of IL-4, IL-13, and IL-5. 相似文献
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Role of GATA-3 in allergic diseases 总被引:3,自引:0,他引:3
Barnes PJ 《Current molecular medicine》2008,8(5):330-334
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Cutting edge: chromatin remodeling at the IL-4/IL-13 intergenic regulatory region for Th2-specific cytokine gene cluster 总被引:4,自引:0,他引:4
Takemoto N Kamogawa Y Jun Lee H Kurata H Arai KI O'Garra A Arai N Miyatake S 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(12):6687-6691
During the differentiation of naive Th cells into Th2 effector cells, the entire IL-4/IL-13 locus is remodeled into an accessible chromatin conformation. Here we show that ectopic expression and activation of Stat6 or GATA-3 in Th cells developing under Th1-polarizing conditions lead to the induction of chromatin remodeling not only at the flanking regions of the IL-4 and IL-13 genes but also at the IL-4/IL-13 intergenic regulatory region for the IL-4/IL-13/IL-5 gene cluster. Furthermore, we demonstrate that GATA-3 and another Th2-specific, inducible protein complex interact with the IL-4/IL-13 intergenic DNase I hypersensitive region specifically in Th2 cells. 相似文献
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Inhibition of Th2 differentiation and GATA-3 expression by BCL-6 总被引:6,自引:0,他引:6
Kusam S Toney LM Sato H Dent AL 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(5):2435-2441