Nicotine protects against ulcerative colitis through regulating microRNA-124 and STAT3

OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis,the underlying mechanisms remain not well-understood.Our previous finding that nicotine inhibits inflammatory responses through inducing miRNA-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine on UC.METHODS Mi R-124 expression in colon tissues and cells was determined by q-PCR and in situ hybridization.The effect of miR-124 on protective role of nicotine in ulcerative colitis was evaluated in DSS-treated mice and IL-6-treated Caco-2 colon epithelial cells.Expression of p-STAT3/STAT3 was detected by immunohistochemistry and Western blot analysis.RESULTS miR-124 expression is upregulated in colon tissues from patients and DSS-induced colitis.Nicotine treatment further elevated miR-124 level in colon tissues of the mice,in infiltrated lymphocytes and epithelial cells,and augmented miR-124 expression in lymphocytes isolated from human ulcerative colon tissues.Administration of nicotine also reduced weight loss,improved DAI and decreased HE score in DSS-induced colitis.Moreover,knockdown of miR-124 in vivo significantly diminished the beneficial effect of nicotine,and in vitro on IL-6-treated Caco-2 colon epithelial cells.Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6-treated Caco-2 colon epithelial cells and Jurkat human T lymphocytes,in whichmiR-124 knockdown led to increased activation of STAT3.CONCLUSION These data indicated that nicotine exerts its protective action in UC through inducing miR-124 and its effect on STAT3,suggesting that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC.