期刊
JOURNAL OF IMMUNOLOGY
卷 173, 期 3, 页码 2109-2117出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.173.3.2109
关键词
-
类别
资金
- NCI NIH HHS [CA51085, CA98454] Funding Source: Medline
- NIDDK NIH HHS [DK02469, DK53620, DK56938, DK63626] Funding Source: Medline
Arginase is the endogenous inhibitor of inducible NO synthase (iNOS), because both enzymes use the same substrate, L-arginase (Arg). Importantly, arginase synthesizes ornithine, which is metabolized by the enzyme ornithine decarboxylase (ODC) to produce polyamines. We investigated the role of these enzymes in the Citrobacter rodentium model of colitis. Arginase I, iNOS, and ODC were induced in the colon during the infection, while arginase II was not up-regulated. L-Arg supplementation of wild-type mice or iNOS deletion significantly improved colitis, and L-Arg treatment of iNOS(-/-) mice led to an additive improvement. There was a significant induction of IFN-gamma, IL-1, and TNF-alpha mRNA expression in colitis tissues that was markedly attenuated with L-Arg treatment or iNOS deletion. Treatment with the arginase inhibitor S-(2-boronoethyl)-L-cysteine worsened colitis in both wild-type and iNOS(-/-) mice. Polyamine levels were increased in colitis tissues, and were further increased by L-Arg. In addition, in vivo inhibition of ODC with alpha-difluoromethylornithine also exacerbated the colitis. Taken together, these data indicate that arginase is protective in C rodentium colitis by enhancing the generation of polyamines in addition to competitive inhibition of iNOS. Modulation of the balance of iNOS and arginase, and of the arginase-ODC metabolic pathway may represent a new strategy for regulating intestinal inflammation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据