Anti-inflammatory mechanism of metformin and its effects in intestinal inflammation and colitis-associated colon cancer
- Authors
- Koh, Seong-Joon; Kim, Jung Mogg; Kim, In-Kyoung; Ko, Su Hyuk; Kim, Joo Sung
- Issue Date
- Mar-2014
- Publisher
- WILEY-BLACKWELL
- Keywords
- colitis; inflammatory bowel disease; metformin; NF-kappa B
- Citation
- JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, v.29, no.3, pp.502 - 510
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
- Volume
- 29
- Number
- 3
- Start Page
- 502
- End Page
- 510
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/160498
- DOI
- 10.1111/jgh.12435
- ISSN
- 0815-9319
- Abstract
- Background and AimThe aim of this study is to evaluate the effect of metformin on intestinal inflammation. MethodsCOLO205 cells were pretreated with metformin and stimulated with tumor necrosis factor (TNF)-. Expression of interleukin (IL)-8 was determined by luciferase assay and real-time PCR. Inhibitor of kappaB (IB) phosphorylation/degradation and adenosine monohosphate-activated protein kinase (AMPK) activity were evaluated by Western blotting. DNA-binding activity of transcription factor nuclear factor-kappaB (NF-B) was assessed by electrophoretic mobility shift assay. In an acute colitis model, mice were given 4% dextran sulfate sodium (DSS) for 5 days. IL-10(-/-) mice were used to evaluate the effect of metformin on chronic colitis. In an inflamation-associated tumor model, mice were given a single intraperitoneal injection of azoxymethane followed by three cycles of 2% DSS for 5 days and 2 weeks of free water consumption. ResultsMetformin significantly inhibited IL-8 induction in COLO 205 cells stimulated with TNF-. Metformin attenuated IB phosphorylation and NF-B DNA-binding activity. Administration of metformin significantly reduced the severity of DSS-induced colitis. In addition, DSS-induced IB kinase (IKK) activation was significantly reduced in mice treated with metformin. Metformin significantly attenuated the severity of colitis in IL-10(-/-) mice, induced AMPK activity in intestinal epithelial cells, and inhibited the development of colitic cancer in mice. ConclusionsThese results indicate that metformin suppresses NF-B activation in intestinal epithelial cells and ameliorates murine colitis and colitis-associated tumorigenesis in mice, suggesting that metformin could be a potential therapeutic agent for the treatment of inflammatory bowel disease.
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