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诱导型 microRNA-223 下调通过靶向 STAT3 促进巨噬细胞中 TLR 触发的 IL-6 和 IL-1β 的产生。

Inducible microRNA-223 down-regulation promotes TLR-triggered IL-6 and IL-1β production in macrophages by targeting STAT3.

机构信息

Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.

出版信息

PLoS One. 2012;7(8):e42971. doi: 10.1371/journal.pone.0042971. Epub 2012 Aug 24.

DOI:10.1371/journal.pone.0042971
PMID:22937006
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3427313/
Abstract

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.

摘要

微小 RNA 是一类小的非编码 RNA 分子，通过翻译抑制或 mRNA 降解来调节基因表达。微小 RNA 在先天和适应性免疫反应的调节中起着关键作用，包括 TLR 触发的炎症反应。在这里，我们报道在脂多糖 (LPS) 或多聚 (I∶C) 刺激激活期间，小鼠巨噬细胞中的微小 RNA-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因子 3 (STAT3) 的激活，STAT3 是 miR-223 的直接靶标，从而促进促炎细胞因子 IL-6 和 IL-1β 的产生，但不促进 TNF-α的产生。有趣的是，发现 IL-6 是 LPS 刺激后 miR-223 表达降低的主要因素，形成正反馈环来调节 IL-6 和 IL-1β。在此，我们的发现提供了一个新的解释，说明了 TLR 触发的巨噬细胞激活后 IL-6 产生的调节的分子机制。

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