Abstract
IntroductionThe 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.Materials and MethodsExcept 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.ResultsmiR‐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.ConclusionsThe 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.
Highlights
The pathogenesis of inflammatory bowel disease (IBD) has not yet been clarified and is closely related to several proinflammatory factors
The upregulation of miR-223 by agomir administration alleviated colonic inflammation in a dextran sodium sulfate (DSS)-induced colitis model, which was likely mediated by inhibiting the production of proinflammatory cytokines via the IL-6/STAT3 signaling pathway
We found that the clinical signs of experimental colitis were improved, MPO and proinflammatory cytokines (TNF-α, IL-6, IL-17) were downregulated and antiinflammatory cytokine (IL-10) were upregulated after administration of the miR-223 agomir, and these changes were reversed after administration of the miR-223 antagomir
Summary
The pathogenesis of inflammatory bowel disease (IBD) has not yet been clarified and is closely related to several proinflammatory factors. MicroRNA-233 (miR-223) might be involved in the development of IBD; the mechanism underlying its pathogenesis is unclear. 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. The pathogenesis of IBD has not yet been clarified and is correlated with complex interactions between susceptibility genes, environmental factors, immunity and inflammation [1]. MicroRNA-233 (miR-223) is a crucial regulator of innate immunity, including myeloid differentiation and the function of neutrophils and macrophages [2]. Aberrant immune activation is a key trigger in the development of chronic mucosal inflammation in IBD [4]. MiR-223 could be a biomarker of IBD to assess disease activity, suggesting that miR-223 is a therapeutic target in IBD
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