The transcription factor GFI1 negatively regulates NLRP3 inflammasome activation in macrophages
The transcription factor GFI1 negatively regulates NLRP3 inflammasome activation in macrophages
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DOI：
10.1016/j.febslet.2014.10.025
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发表时间：
2014-11
期刊：
影响因子：
3.5
通讯作者：
Liuluan Zhu;Qingcai Meng;Shuntao Liang;Ya-luan Ma;Rui Li;Guoli Li;H. Zeng
中科院分区：
文献类型：
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作者：
Liuluan Zhu;Qingcai Meng;Shuntao Liang;Ya-luan Ma;Rui Li;Guoli Li;H. Zeng
Toll样受体（TLR）激活下游的白细胞介素-1 β（IL-1β）分泌在转录和翻译后水平受到严格控制。NLRP 3炎性体参与pro-IL-1β的成熟，其中NLRP 3表达被鉴定为炎性体活化的限制因子。以前，我们已经证明了锌指蛋白GFI 1抑制pro-IL-1β转录。在这里，我们表明GFI 1抑制巨噬细胞中的NLRP 3炎性体活化和IL-1β分泌。GFI 1通过两种机制抑制Nlrp 3的转录：（1）通过与Nlrp 3启动子中的Gli反应元件1（GRE 1）结合;（2）通过拮抗核因子-κB（NF-κB）的转录活性。因此，GFI 1在转录和翻译后水平负调节TLR介导的IL-1β产生。
Interleukin-1β (IL-1β) secretion downstream of Toll-like receptor (TLR) activation is tightly controlled at the transcriptional and post-translational levels. NLRP3 inflammasome is involved in the maturation of pro-IL-1β, with NLRP3 expression identified as the limiting factor for inflammasome activation. Previously, we had demonstrated that the zinc-finger protein GFI1 inhibits pro-IL-1β transcription. Here, we show that GFI1 inhibits NLRP3 inflammasome activation and IL-1β secretion in macrophages. GFI1 suppressedNlrp3transcription via two mechanisms: (1) by binding to the Gli-responsive element 1 (GRE1) in theNlrp3promoter; and (2) by antagonizing the nuclear factor-κB (NF-κB) transcriptional activity. Thus, GFI1 negatively regulates TLR-mediated IL-1β production at both transcriptional and post-translational levels.