2008年10月
FR167653, a p38 mitogen-activated protein kinase inhibitor, aggravates experimental colitis in mice
WORLD JOURNAL OF GASTROENTEROLOGY
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- 巻
- 14
- 号
- 38
- 開始ページ
- 5851
- 終了ページ
- 5856
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.3748/wjg.14.5851
- 出版者・発行元
- W J G PRESS
AIM: To investigate the effects of FR167653 on the development of dextran sulfate sodium (DSS)-induced colitis in mice.
METHODS: BALB/c mice were fed rodent chow containing 3.5% (wt/wt) DSS. The recipient mice underwent intra-peritoneal injection of vehicles or FR167653 (30 mg/kg per day). The mice were sacrificed on day 14, and the degree of colitis was assessed. Immunohistochemical analyses for CD4(+) T cell and F4/80(+) macrophage infiltration were also performed. Mucosal cytokine expression was analyzed by RT-PCR.
RESULTS: The body weight loss was more apparent in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. The colon length was shorter in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. Disease activity index and histological colitis score were significantly higher in FR167653- than in vehicle-treated DSS animals. Microscopically, mucosal edema, cellular infiltration (CD4 T cells and F4/80 macrophages), and the disruption of the epithelium were much more severe in FR167653-treated mice than in controls. Mucosal mRNA expression for interleukin-1 beta (IL-1 beta) and tumor necrosis factor-a (TNF-alpha) were found to be markedly reduced in FR167653-treated DSS mice.
CONCLUSION: Treatment with FR167653 aggravated DSS colitis in mice, This effect was accompanied by a reduction of mucosal IL-1 beta and TNF-alpha expression, suggesting a role of p38 mitogen-activated protein kinase (MAPK)-mediated proinflammatory cytokine induction in host defense mechanisms. (C) 2008 The WJG Press. All rights reserved.
METHODS: BALB/c mice were fed rodent chow containing 3.5% (wt/wt) DSS. The recipient mice underwent intra-peritoneal injection of vehicles or FR167653 (30 mg/kg per day). The mice were sacrificed on day 14, and the degree of colitis was assessed. Immunohistochemical analyses for CD4(+) T cell and F4/80(+) macrophage infiltration were also performed. Mucosal cytokine expression was analyzed by RT-PCR.
RESULTS: The body weight loss was more apparent in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. The colon length was shorter in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. Disease activity index and histological colitis score were significantly higher in FR167653- than in vehicle-treated DSS animals. Microscopically, mucosal edema, cellular infiltration (CD4 T cells and F4/80 macrophages), and the disruption of the epithelium were much more severe in FR167653-treated mice than in controls. Mucosal mRNA expression for interleukin-1 beta (IL-1 beta) and tumor necrosis factor-a (TNF-alpha) were found to be markedly reduced in FR167653-treated DSS mice.
CONCLUSION: Treatment with FR167653 aggravated DSS colitis in mice, This effect was accompanied by a reduction of mucosal IL-1 beta and TNF-alpha expression, suggesting a role of p38 mitogen-activated protein kinase (MAPK)-mediated proinflammatory cytokine induction in host defense mechanisms. (C) 2008 The WJG Press. All rights reserved.
- リンク情報
- ID情報
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- DOI : 10.3748/wjg.14.5851
- ISSN : 1007-9327
- Web of Science ID : WOS:000260223300010