miR-223 improves intestinal inflammation through inhibiting the IL-6/STAT3 signaling pathway in dextran sodium sulfate-induced experimental colitis.

The pathogenesis of inflammatory bowel disease (IBD) has not yet been clarified and is closely related to several pro-inflammatory factors. MicroRNA-233 (miR-223) might be involved in the development of IBD; however, the mechanism underlying its pathogenesis is unclear. In this study, we attempted to determine the role of miR-223 in dextran sodium sulfate (DSS)-induced colitis and explore the involvement of the IL-6/STAT3 pathway in the development of intestinal mucosal inflammation. Except control (WT) group, male C57BL/6 mice were provided DSS, then treated for with miR-223 agomir or antagomir including DSS group, DSS + miR-223 agomir (DSS + A) group, and DSS + miR-223 antagomir (DSS + AN) group. The colitis symptoms were observed, the disease activity index (DAI) score were recorded daily, and colonic inflammation was evaluated by histopathological scoring. The expression of myeloperoxidase (MPO), cytokines and IL-6/STAT3 pathway-related proteins were measured. miR-223 expression in the terminal ileum and colon was increased in the DSS group compared with the WT group. Colitis symptoms were significantly alleviated in the DSS + A group and exacerbated in the DSS + AN group after administration of the miR-223 agomir and antagomir, respectively. MPO, tumor necrosis factor-α, IL-6, and IL-17 were decreased and IL-10 was increased in the DSS + A group, but these changes were reversed in the DSS + AN group. Gp130, p-STAT3, Bcl-2, and Bcl-xl in the colon declined in the DSS + A group, but these levels increased in the DSS + AN group. The upregulation of miR-223 by agomir administration alleviated colonic inflammation in a DSS-induced colitis model, which was likely mediated by inhibiting the production of pro-inflammatory cytokines via the IL-6/STAT3 signaling pathway. These findings provide evidence that miR-223 might have potential therapeutic implications in IBD.

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