Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China.
Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China.
Front Immunol. 2022 Feb 10;13:779770. doi: 10.3389/fimmu.2022.779770. eCollection 2022.
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 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 and . 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 infection . 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.
炎症是一把双刃剑，它可以被各种 PAMP 诱导，从而控制感染入侵病原体或损伤。炎症反应需要严格和精确的控制和调节。microRNAs（miRNAs）是调节基因表达的小非编码 RNA 分子，其作用包括翻译抑制或 mRNA 降解。然而，miRNAs 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 微阵列鉴定了在 flagellin 处理和单独培养基之间，在鼠骨髓来源的树突状细胞（BMDCs）中差异表达的 miRNAs。我们发现，flagellin 刺激可下调 BMDCs 和脾 DCs 中的 miR-5112 表达，并。miR-5112 的过表达可降低炎性细胞因子的产生，同时减少 flagellin 刺激的 BMDCs 中的 IKKγ。我们证明 miR-5112 可直接靶向 IKKγ 以抑制炎性细胞因子的产生。此外，miR-5112 可抑制 flagellin 或 LPS 感染诱导的炎症反应。有趣的是，miR-5112 还可以抑制炎症反应并减轻 C57BL/6 小鼠中的葡聚糖硫酸钠（DSS）诱导的结肠炎。这些结果表明，miR-5112 可能是细菌感染和 DSS 诱导的结肠炎模型的一种新的治疗靶标。
