5-Fluorouracil induces diarrhea with changes in the expression of inflammatory cytokines and aquaporins in mouse intestines.
5-Fluorouracil induces diarrhea with changes in the expression of inflammatory cytokines and aquaporins in mouse intestines.
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DOI：
10.1371/journal.pone.0054788
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Narita M
中科院分区：
文献类型：
--
作者：
Sakai H;Sagara A;Matsumoto K;Hasegawa S;Sato K;Nishizaki M;Shoji T;Horie S;Nakagawa T;Tokuyama S;Narita M
尽管5-氟尿嘧啶（5-FU）引起的腹泻的机制尚不清楚，但越来越多的证据表明，粘膜免疫系统和水通道蛋白（AQP）的变化可能在其发病机制中发挥作用。因此，我们研究了5-FU诱导腹泻的小鼠肠道中炎症细胞因子和AQP基因表达的可能变化。在本研究中，给予 5-FU 后出现腹泻的小鼠整个结肠中编码炎症细胞因子 TNF-α、IL-1β、IL-6、IL-17A 和 IL-22 的 mRNA 表达显着增加。相反，IFNγ的基因表达仅在远端结肠中上调。服用依那西普后，这些增加显着减少。然而，依那西普未能恢复 5-FU 引起的腹泻。另一方面，AQP 4 和 8 的基因明显存在于结肠中，并且通过 5-FU 处理，这些基因在肠道中的表达显着降低。依那西普并未逆转这些下降。这些发现表明 TNF-α 中和对 5-FU 引起的急性腹泻和 AQP 受损没有影响，但显着减少了几种炎症细胞因子。
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.
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影响因子：
3.5
作者：
Okada, S;Misaka, T;Abe, K
通讯作者：
Abe, K
影响因子：
29.4
作者：
Strater, J;Wellisch, I;Moller, P
通讯作者：
Moller, P
影响因子：
3.6
作者：
Hardin, JA;Wallace, LE;Beck, PL
通讯作者：
Beck, PL
影响因子：
3
作者：
Logan, Richard M.;Stringer, Andrea M.;Keefe, Dorothy M. K.
通讯作者：
Keefe, Dorothy M. K.
水通道蛋白 5 在抗原诱导的小鼠气道炎症和粘液过度生成中的作用。
影响因子：
5.3
作者：
Shen Y;Wang Y;Chen Z;Wang D;Wang X;Jin M;Bai C
通讯作者：
Bai C