title: 5-Fluorouracil induces diarrhea with changes in the expression of inflammatory cytokines and aquaporins in mouse intestines.
abstract: 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.
authors: Department of Pharmacology, Hoshi University, Tokyo, Japan. sakai@hoshi.ac.jp
authors: Hiroyasu
authors: H
authors: Sakai
authors: Atsunobu
authors: A
authors: Sagara
authors: Kenjiro
authors: K
authors: Matsumoto
authors: Satoshi
authors: S
authors: Hasegawa
authors: Ken
authors: K
authors: Sato
authors: Maiko
authors: M
authors: Nishizaki
authors: Tetsuro
authors: T
authors: Shoji
authors: Syunji
authors: S
authors: Horie
authors: Takayuki
authors: T
authors: Nakagawa
authors: Shogo
authors: S
authors: Tokuyama
authors: Minoru
authors: M
authors: Narita
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D020346:Aquaporins / Q000235:genetics*; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D003967:Diarrhea / Q000139:chemically induced* / Q000235:genetics* / Q000276:immunology; D000068800:Etanercept; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology; D018836:Inflammation Mediators; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology; D008297:Male; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage
chemical_list: D000964:Antimetabolites, Antineoplastic; D020346:Aquaporins; D016207:Cytokines; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept; D005472:Fluorouracil
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