Inducible microRNA-223 down-regulation promotes TLR-triggered IL-6 and IL-1β production in macrophages by targeting STAT3.
Inducible microRNA-223 down-regulation promotes TLR-triggered IL-6 and IL-1β production in macrophages by targeting STAT3.
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DOI：
10.1371/journal.pone.0042971
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Chen Q;Wang H;Liu Y;Song Y;Lai L;Han Q;Cao X;Wang Q
MicroRNAs是一种小的非编码RNA分子，通过翻译抑制或mRNA降解来调节基因的表达。MicroRNAs在调节先天免疫反应和获得性免疫反应，包括TLR触发的炎症反应中发挥着关键作用。在此，我们报道了小鼠巨噬细胞在脂多糖(LPS)或Poly(I：C)刺激下的激活过程中，microRNA-223(miR-223)的表达显著降低。诱导的miR-223下调导致信号转导和转录激活子3(STAT3)的激活，而信号转导和转录激活因子3是miR-223直接靶向的信号转导和转录激活因子，从而促进促炎细胞因子IL-6和IL-1β的产生，而不是肿瘤坏死因子-α。有趣的是，IL-6被发现是导致内毒素刺激后miR-223表达下降的主要因素，并形成了调节IL-6和IL-1β的正反馈环。在这里，我们的发现提供了一种新的解释，描述了TLR触发的巨噬细胞激活后调节IL-6产生的分子机制。
MicroRNAs are small non-coding RNA molecules that regulate gene expression by either translational inhibition or mRNA degradation. MicroRNAs play pivotal roles in the regulation of both innate and adaptive immune responses, including TLR-triggered inflammatory response. Here we reported that the expression of microRNA-223 (miR-223) was significantly decreased in murine macrophages during activation by lipopolysaccharide (LPS) or poly (I∶C) stimulation. The inducible miR-223 down-regulation resulted in the activation of signal transducer and activator of transcription 3 (STAT3), which is directly targeted by miR-223, thus promoting the production of pro-inflammatory cytokines IL-6 and IL-1β, but not TNF-α. Interestingly, IL-6 was found to be a main factor in inducing the decrease in miR-223 expression after LPS stimulation, which formed a positive feedback loop to regulate IL-6 and IL-1β. Herein, our findings provide a new explanation characterizing the molecular mechanism responsible for the regulation of IL-6 production after TLR-triggered macrophage activation.
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