title: Metformin Ameliorates Inflammatory Bowel Disease by Suppression of the STAT3 Signaling Pathway and Regulation of the between Th17/Treg Balance.
abstract: OBJECTIVE
  Metformin is used to treat type 2 diabetes. We sought to determine whether metformin reduces inflammation, by regulating p-signal transducer and activator of transcription 3 (STAT3) expression and T-helper 17 (Th17) cell proliferation, in a mouse model of inflammatory bowel disease (IBD).
  
  
  METHODS
  IBD mice were administered metformin for 16 days and their tissues were analyzed. AMP-activated protein kinase (AMPK), the mammalian target of rapamycin (mTOR), p-STAT3 and p-STAT5 in the spleen and lymph nodes were detected using immunohistochemistry and confocal microscopy. Gene expression was determined using quantitative PCR assays, and protein expression levels were measured using western blotting and enzyme-linked immunosorbent assays. Human HT-29 cell proliferation was evaluated using MTT assays.
  
  
  RESULTS
  Metformin reduced disease activity index scores and inhibited weight loss. Metformin also decreased the colonic histological score and inflammatory mediators and increased colon lengths increased. Treatment with metformin inhibited the expression of interleukin (IL)-17, p-STAT3, and p-mTOR. In contrast, metformin treatment increased expression levels of p-AMPK and Foxp3. In addition, expression of inflammatory cytokines decreased in a dose-dependent manner in inflamed human HT-29 cells cultured with metformin at various concentrations.
  
  
  CONCLUSIONS
  Metformin attenuates IBD severity and reduces inflammation through the inhibition of p-STAT3 and IL-17 expression. Our results have increased our understanding of this chronic inflammatory disease, and support the strategy of using p-STAT3 inhibitors to treat IBD.
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea; The Laboratory of Immune Network, CRCID, The Catholic University, Seoul, Republic of Korea.
authors.forename: Seon-Yeong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Yang
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Gachon University of Medicine and Science, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 406-799, Korea.
authors.forename: Dong-Yun
authors.initials: DY
authors.lastname: Shin
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea; The Laboratory of Immune Network, CRCID, The Catholic University, Seoul, Republic of Korea.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism*; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D008687:Metformin; D058570:TOR Serine-Threonine Kinases