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BACKGROUND AND AIMS MicroRNA (miR)-497 is downregulated in several inflammatory diseases, excluding inflammatory bowel disease (IBD). The aim of this study is to evaluate whether miR-497 inhibits gut inflammation both in vivo and in vitro. METHODS The 3% dextran sulphate sodium (DSS) was used to induce experimental colitis, while 1 μg/ml lipopolysaccharide (LPS) was for RAW264.7 cell damage.Colitis severity was evaluated by disease activity index (DAI), colon length, histopathologic injury, etc. The nuclear transcription factor NF-κB activity in colon tissues was also estimated by western blot. Then, the quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the expression levels of miR-497, pro-inflammatory cytokines and chemokines in colon tissues and RAW264.7 cells. Furthermore, the activity of Wnt/β-catenin pathway was determined by western blot and TOP/FOP-flash reporter assays. RESULTS The level of miR-497 was reduced in inflamed mucosa from IBD patients, mice with colitis and LPS-treated RAW264.7 cells. miR-497 knockout (miR-497 KO) mice were more susceptible to DSS-induced colitis, with increased inflammatory response, compared with control mice. Furthermore, the overexpression of miR-497 reduced the release of pro-inflammatory cytokines and chemokines in LPS-treated RAW264.7 cells. Finally, we found that miR-497 inhibited inflammation through Wnt/β-catenin pathway both in vitro and in vivo. CONCLUSION Our data indicate that miR-497 inhibits inflammation in DSS-induced IBD model mice and LPS-induced RAW264.7 cells by inhibiting the activation of NF-κB pathway and the release of cytokines, indicating that miR-497 plays a key role in the progression of IBD. Thus, therapeutic regulation of miR-497 expression may be beneficial for the treatment of IBD.