title: Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3.
abstract: 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 miR-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine against UC. Our present study found that miR-124 expression is upregulated in colon tissues from UC patients and DSS colitis mice. Nicotine treatment further augmented miR-124 expression in lymphocytes isolated from human ulcerative colonic mucosa and ulcerative colon tissues from DSS mice, both in infiltrated lymphocytes and epithelial cells. Moreover, knockdown of miR-124 significantly diminished the beneficial effect of nicotine on murine colitis and 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 cells and Jurkat human T lymphocytes, in which miR-124 knockdown led to increased activation of STAT3. Blocking STAT3 activity alone is beneficial for DSS colitis and also abolished nicotine's protective effect in this model. These data indicate that nicotine exerts its protective action in UC through inducing miR-124 and inhibiting STAT3, and suggest that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC.
  
  
  
  Nicotine upregulates miR-124 expression in ulcerative colon tissues and cells. MiR-124 is required for the protective role of nicotine in DSS colitis mice and epithelial cells. The protective effect of nicotine in murine DSS colitis depends on blocking STAT3 activation. MiR-124 mediates the inhibitory role of nicotine on STAT3/p-STAT3. Targeting miR-124 and STAT3 represents a novel approach for treating ulcerative colitis.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Wan
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Colorectal Surgery, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200095, People's Republic of China.
authors.forename: Tingyu
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China.
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Department of Colorectal Surgery, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200095, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Du
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China. dfsu@smmu.edu.cn.
authors.forename: Ding-Feng
authors.initials: DF
authors.lastname: Su
authors.affiliation: Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, 215123, People's Republic of China. yyl@ism.cams.cn.
authors.forename: Yili
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China. lxflying@aliyun.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D009538:Nicotine; D016264:Dextran Sulfate
keywords: Colon epithelial cell; Human T lymphocytes; MicroRNA-124; Nicotine; Ulcerative colitis; p-STAT3