Transcription factor Fli-1 positively regulates lipopolysaccharide-induced interleukin-27 production in macrophages
Transcription factor Fli-1 positively regulates lipopolysaccharide-induced interleukin-27 production in macrophages
复制标题
转录因子 Fli-1 正向调节脂多糖诱导的巨噬细胞中白细胞介素 27 的产生。
DOI：
10.1016/j.molimm.2016.02.006
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发表时间：
2016-03-01
影响因子：
3.6
通讯作者：
An, Huazhang
中科院分区：
文献类型：
--
作者：
Gao, Peng;Yuan, Ming;An, Huazhang
IL-27是TLR 4激活的天然免疫的重要调节因子。在TLR 4激活的先天免疫中调节IL-27产生的机制在很大程度上仍不清楚。在这里，我们表明，转录因子Fli-1在蛋白水平的表达增加，在巨噬细胞LPS刺激后。Fli-1过表达增加巨噬细胞中LPS激活的IL-27产生。一致地，Fli-1敲除抑制了巨噬细胞中LPS诱导的IL-27的产生。染色质免疫沉淀（ChIP）分析显示Fli-1结合IL-27 p28亚基的启动子。进一步的实验表明Fli-1与p28基因转录起始位点上游-250 ~-150bp之间的区域结合，增加p28基因启动子控制的转录。这些结果表明，Fli-1通过促进IL-27 p28基因的转录，在TLR 4激活的免疫应答中正向调节IL-27的产生。(C)2016爱思唯尔有限公司版权所有
IL-27 is an important regulator of TLR4-activated innate immune. The mechanism by which IL-27 production is regulated in TLR4-activated innate immune remains largely unclear. Here we show that expression of transcription factor Fli-1 at protein level is increased in macrophages following LPS stimulation. Fli-1 overexpression increases LPS-activated IL-27 production in macrophages. Consistently, Fli-1 knockdown inhibits LPS-induced IL-27 production in macrophages. Chromatin immunoprecipitation (ChIP) assay reveals that Fli-1 binds the promoter of IL-27 p28 subunit. Further experiments manifest that Fli-1 binds the region between -250 and -150 bp upstream of the transcriptional start site of p28 gene and increases p28 gene promoter-controlled transcription. These results demonstrate that Fli-1 positively regulates IL-27 production in TLR4-activated immune response by promoting transcription of IL-27 p28 gene. (C) 2016 Elsevier Ltd. All rights reserved.