MicroRNA-5112 Targets IKKγ to Dampen the Inflammatory Response and Improve Clinical Symptoms in Both Bacterial Infection and DSS-Induced Colitis.
MicroRNA-5112 Targets IKKγ to Dampen the Inflammatory Response and Improve Clinical Symptoms in Both Bacterial Infection and DSS-Induced Colitis.
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MicroRNA-5112 靶向 IKKγ 抑制炎症反应并改善细菌感染和 DSS 诱发的结肠炎的临床症状
DOI：
10.3389/fimmu.2022.779770
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发表时间：
2022
影响因子：
7.3
通讯作者：
Pan Z
中科院分区：
文献类型：
--
作者：
Kang X;Jiao Y;Zhou Y;Meng C;Zhou X;Song L;Jiao X;Pan Z
炎症是一把双刃剑，可以由各种PAMPs诱导，通过入侵病原体或损伤来控制感染。炎症反应需要严格和精确的控制和调节。MicroRNAs （miRNAs）是一种小的非编码RNA分子，通过翻译抑制或mRNA降解来调节基因表达。然而，mirna在鞭毛蛋白（TLR5的配体）诱导的炎症中的作用尚未完全确定。在这项研究中，我们使用miRNA芯片鉴定了鞭毛蛋白处理和单独培养基中小鼠骨髓源性树突状细胞（bmdc）中差异表达的miRNA。我们发现鞭毛蛋白刺激在体外和体内下调bmdc和脾脏dc中miR-5112的表达。在鞭毛蛋白刺激的BMDCs中，miR-5112的过表达减少了炎症细胞因子的产生，并伴有IKKγ的减少。我们证明miR-5112可以直接靶向IKKγ抑制炎症细胞因子的产生。此外，miR-5112在体内抑制鞭毛蛋白或沙门氏菌感染诱导的炎症反应。有趣的是，miR-5112还可以抑制C57BL/6小鼠的炎症反应并减轻葡聚糖硫酸钠（DSS）诱导的结肠炎。这些结果表明，miR-5112可能成为细菌感染和dss诱导结肠炎模型的新治疗靶点。
Inflammation is a double-edged sword that can be induced by various PAMPs, resulting in the control of infection by invading pathogens or injuries. The inflammatory response requires strict and precise control and regulation. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression via translational inhibition or mRNA degradation. However, the role of miRNAs in inflammation induced by flagellin (ligand of TLR5) has yet to be fully determined. In this study, we identified differentially expressed miRNAs in murine bone marrow-derived dendritic cells (BMDCs) between flagellin treatment and medium alone using miRNA microarray. We found that flagellin stimulation downregulated miR-5112 expression in BMDCs and spleen DCs in vitro and in vivo. The overexpression of miR-5112 decreased inflammatory cytokine production, accompanied by a reduction of IKKγ in flagellin-stimulated BMDCs. We demonstrated that miR-5112 could directly target IKKγ to inhibit inflammatory cytokine production. Furthermore, miR-5112 inhibited the inflammatory response induced by flagellin or Salmonella infection in vivo. Interestingly, miR-5112 could also dampen the inflammatory response and alleviate dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. These results suggest that miR-5112 could be a novel therapeutic target for both bacterial infection and DSS-induced colitis model.
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3.7
作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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