Open Access5-Fluorouracil Induces Diarrhea with Changes in the Expression of Inflammatory Cytokines and Aquaporins in Mouse Intestines
Author(s) -
Hiroyasu Sakai,
Atsunobu Sagara,
Kenjiro Matsumoto,
S. Hasegawa,
Ken Sato,
Maiko Nishizaki,
Tetsuro Shoji,
Syunji Horie,
Takayuki Nakagawa,
Shogo Tokuyama,
Minoru Narita
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0054788
Subject(s) - diarrhea , aquaporin , tumor necrosis factor alpha , immune system , inflammation , etanercept , proinflammatory cytokine , colitis , downregulation and upregulation , pathogenesis , immunology , gene expression , medicine , endocrinology , biology , gene , physiology , biochemistry
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-α, IL-1β, 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 IFNγ 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-α neutralization had no effect on the acutely 5-FU-induced diarrhea and impaired AQPs but reduced dramatically several inflammatory cytokines.