期刊
PLOS ONE
卷 8, 期 1, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0054788
关键词
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资金
- KAKENHI [24790582]
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [24111527, 24790582, 24590118, 23790641] Funding Source: KAKEN
Although the mechanisms of 5-fluorouracil (5-FU)-induced diarrhea remain unclear, accumulating evidence has indicated that changes in the mucosal immune system and aquaporins (AQPs) may play a role in its pathogenesis. Therefore, we investigated the possible changes in the gene expression of inflammatory cytokines and AQPs in the intestines of mice with 5-FU-induced diarrhea. In the present study, the expressions of mRNAs that encode inflammatory cytokines, TNF-alpha, IL-1 beta, IL-6, Il-17A and IL-22, were significantly increased throughout the entire colon of mice that exhibited diarrhea following 5-FU administration. In contrast, the gene expression of IFN gamma was upregulated only in the distal colon. These increases were significantly reduced by the administration of etanercept. However, 5-FU-induced diarrhea was not recovered by etanercept. On the other hand, the genes for AQPs 4 and 8 were markedly present in the colon, and these expressions in the intestines were significantly decreased by treatment with 5-FU. These decreases were not reversed by etanercept. These findings suggest TNF-alpha neutralization had no effect on the acutely 5-FU-induced diarrhea and impaired AQPs but reduced dramatically several inflammatory cytokines.
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