Effects of indoleamine 2,3-dioxygenases in carbon tetrachloride-induced hepatitis model of rats
Effects of indoleamine 2,3-dioxygenases in carbon tetrachloride-induced hepatitis model of rats
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DOI：
10.1002/cbf.2803
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发表时间：
2012-06-01
影响因子：
3.6
通讯作者：
Lv, Zhongwei
中科院分区：
文献类型：
--
作者：
Li, Dan;Cai, Haidong;Lv, Zhongwei
吲哚胺2，3-双加氧酶（IDO）将色氨酸转化为l-犬尿氨酸，并且它被认为是促进耐受性和抑制适应性免疫的相关分子。在本研究中，为了研究IDO在四氯化碳（CCl 4）诱导的肝炎模型中的作用，通过测定犬尿氨酸浓度来确认模拟组、对照组和1-甲基-d-色氨酸（1-MT）处理组中的IDO酶活性水平。注射CCl 4后，1-MT处理组大鼠血清丙氨酸氨基转移酶水平显著高于模拟组和对照组。在CCl 4诱导的肝炎模型中，肿瘤坏死因子-a（TNF-α）在肝损伤的发展中至关重要。1-MT处理组大鼠肝脏TNF-α mRNA的表达和分泌水平较空白对照组和空白对照组明显增强。此外，通过ELISA分析模拟组、对照组和1-MT治疗组大鼠经CCl 4处理后的细胞因子和趋化因子水平，发现1-MT治疗组大鼠的白细胞介素-6水平升高。结论：IDO缺乏可加重CCl_4诱导的肝炎肝损伤，其作用可能与TNF-α和IL-6有关。版权所有（c）2012约翰威利父子有限公司
Indoleamine 2,3-dioxygenase (IDO) converts tryptophan to l-kynurenine, and it is noted as a relevant molecule in promoting tolerance and suppressing adaptive immunity. In this study, to investigate the effects of IDO in carbon tetrachloride (CCl4)induced hepatitis model, the levels of IDO enzymic activities in the mock group, the control group and the 1-methyl-d-tryptophan (1-MT)treated group were confirmed by determination of l-kynurenine concentrations. Serum alanine aminotransferase levels in 1-MT-treated rats after CCl4 injection significantly increased compared with those in mock and control groups. In CCl4-induced hepatitis models, tumour necrosis factor-a (TNF-a) is critical in the development of liver injury. The mRNA expression and secretion levels of TNF-a in the liver from 1-MT-treated rats were more enhanced compared with those in the mock and the control groups. Moreover, the levels of cytokine and chemokine from mock, control group and 1-MT-treated rats after treated with CCl4 were analyzed by ELISA, and the level of interleukin-6 was found to increase in 1-MT-treated rats. It was concluded that the deficiency of IDO exacerbated liver injury in CCl4-induced hepatitis and its effect may be connected with TNF-a and interleukin-6. Copyright (c) 2012 John Wiley & Sons, Ltd.