共查询到20条相似文献,搜索用时 15 毫秒
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IFN-alpha induces the human IL-10 gene by recruiting both IFN regulatory factor 1 and Stat3 总被引:1,自引:0,他引:1
Ziegler-Heitbrock L Lötzerich M Schaefer A Werner T Frankenberger M Benkhart E 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(1):285-290
The anti-inflammatory cytokine IL-10 can be induced by type I IFNs, but the molecular mechanisms involved have remained elusive. With in silico analysis of the human IL-10 promoter we identified a module consisting of an IFN regulatory factor 1 (IRF-1) site and a Stat3 site. We demonstrate that IFN-alpha will induce the binding of IRF-1 and Stat3 to the respective motifs. Mutational analysis revealed that inactivation of the IRF-1 motif substantially reduces trans-activation from 5- to 2-fold and that inactivation of the Stat3 motif completely ablates trans-activation by IFN-alpha. The dominant role of Stat3 in this module was confirmed with the blockade of trans-activation by a dominant negative Stat3. By contrast, Stat1 contributes a minor proportion to the DNA binding to the Stat site, and overexpression will counteract Stat3-mediated trans-activation. The data show that IFN-alpha induces the IL-10 gene via a module consisting of interdependent IRF-1 and Stat3 motifs. Of note, LPS-induced trans-activation does not target this module, since it is independent of the IRF-1 motif but completely depends on Stat3. 相似文献
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An IL-2 response element in the human IL-2 receptor alpha chain promoter is a composite element that binds Stat5, Elf-1, HMG-I(Y) and a GATA family protein. 总被引:7,自引:0,他引:7 下载免费PDF全文
Expression of the human interleukin-2 (IL-2) receptor alpha chain gene is potently upregulated by its own ligand, IL-2. In this study, we characterize an essential upstream IL-2 response element that contains both consensus and non-consensus GAS motifs, two putative Ets binding sites (EBS), one of which overlaps the consensus GAS motif, and a GATA motif, which overlaps the non-consensus GAS motif. We demonstrate that although the individual components of this element do not respond to IL-2, together they form a composite element capable of conferring IL-2 responsiveness to a heterologous promoter. Multiple factors including Stat5, Elf-1, HMG-I(Y) and GATA family proteins bind to the IL-2 response element and mutation of any one of these binding sites diminishes the activity of this element. An unidentified Ets family protein binds to the EBS overlapping the consensus GAS motif and appears to negatively regulate the human IL-2R alpha promoter. Thus, IL-2-induced IL-2R alpha promoter activity requires a complex upstream element, which appears to contain binding sites for both positive and negative regulatory factors. 相似文献
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Mehrotra P Riley JP Patel R Li F Voss L Goenka S 《The Journal of biological chemistry》2011,286(3):1767-1776
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Tone M Powell MJ Tone Y Thompson SA Waldmann H 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(1):286-291
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Marylynn Snyder Jianyun Huang Xin-Yun Huang J. Jillian Zhang 《The Journal of biological chemistry》2014,289(43):30082-30089
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