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

Zhen QIN,Yang SUN,Ding-feng SU,Xia LIU

(Department of Pharmacology,Second Military Medical University,Shanghai 200433,China）

T2-20

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

Zhen QIN,Yang SUN,Ding-feng SU,Xia LIU

(Department of Pharmacology,Second Military Medical University,Shanghai 200433,China）

OBJECTIVEAlthough 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.METHODSMiR-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 immuno?histochemistry and Western blot analysis.RESULTSmiR-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,knock?down 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 which miR-124 knockdown led to increased activation of STAT3.CONCLUSIONThese 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.

microRNA-124;nicotine;ulcerative colitis;p-STAT3;human T lymphocytes;colon epithelial cell

The project supported by National Natural Science Foundation of China(81273606,81473259 to XL,81603116 to YS);and National Science and Technology Major Project(2014ZX09J14103-08C to XL)

Xia LIU,Tel:13764083416,E-mail:lxflying@aliyun.com;Ding-feng SU,E-mail:dfsu@smmu.edu.cn