Journal
INFLAMMATION RESEARCH
Volume 60, Issue 8, Pages 727-734Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00011-011-0325-6
Keywords
Ulcerative colitis; DSS-induced colitis; Wortmannin; PI3K/Akt signal pathway; TNF-alpha
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Funding
- National Natural Science Foundation of China [30700351]
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The purpose of this study was to investigate the role of the PI3K/Akt signaling pathway in the pathogenesis of ulcerative colitis (UC). Mucosal biopsy specimens from 54 active UC cases and adjacent normal tissues from 18 colon cancer cases were investigated. Twenty-eight Balb/c mice were randomly divided into four groups. Dextran sulphate sodium (DSS) solution (5%) was used to develop the mouse colitis model. After treatment with wortmannin (a PI3K inhibitor), disease activity index (DAI) and histological score was determined for each group of mice. Expression of phosphorylated Akt (p-Akt) in UC patients and mouse intestinal mucosa was determined by immunohistochemical staining. We also determined the effect of wortmannin on tumor necrosis factor-alpha (TNF-alpha) expression in intestinal biopsy tissues of UC patients and mice with DSS-induced colitis. Wortmannin significantly reduced the level of p-Akt and TNF-alpha in the colitis tissues of UC patients and DSS-treated mice. Wortmannin significantly alleviated the inflammation of colitis as assessed by DAI and histological score in DSS-treated mice. The PI3K/Akt signal transduction pathway is involved in the regulation and release of pro-inflammatory cytokines such as TNF-alpha and plays an important role in the development and progression of UC.
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