Innate immune reactivity of the liver in rats fed a choline-deficient L-amino-acid-defined diet
Innate immune reactivity of the liver in rats fed a choline-deficient L-amino-acid-defined diet
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DOI：
10.3748/wjg.14.6655
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发表时间：
2008-11-21
影响因子：
4.3
通讯作者：
Fukui, Hiroshi
中科院分区：
文献类型：
--
作者：
Kawaratani, Hideto;Tsujimoto, Tatsuhiro;Fukui, Hiroshi
目的：探讨非酒精性脂肪性肝炎（NASH）模型大鼠肝脏中肿瘤坏死因子-α（TNF-alpha）、Toll样受体4（TLR 4）和CD 14的先天免疫反应性。方法：雄性F344大鼠饲喂胆碱缺乏的L-氨基酸定义（CDAA）饲料。喂养4或8周后处死大鼠，取肝脏进行免疫组织化学研究和RNA提取。对肝脏标本进行TNF-α、TLR 4和CD 14免疫染色。逆转录聚合酶链反应（RT-PCR）测定TNF-α、TLR 4和CD 14的基因表达。结果：CDAA-fecl组大鼠血清和肝脏TNF-α水平明显高于对照组，TNF-α、TLR 4和CD 14的免疫组化值和基因表达也随脂肪性肝炎的进展而升高。结论：TNF-α、TLR 4和CD 14在NASH模型中表达增加，提示TLR 4和CD 14介导的内毒素性肝损伤也可能在NASH中发生。(C)2008年，WJG出版社。All rights reserved.
AIM: To investigate the innate immune reactivity of tumor necrosis factor-alpha (TNF-alpha), Toll-like receptor 4 (TLR4), and CD14 in the liver of non-alcoholic steatohepatitis (NASH) model rats.METHODS: Male F344 rats were fed a choline-deficient L-amino-acid-defined (CDAA) diet. The rats were killed after 4 or 8 wk of the diet, and their livers were removed for immunohistochemical investigation and RNA extraction. The liver specimens were immunostained for TNF-alpha, TLR4, and CD14. The gene expressions of TNF-alpha, TLR4, and CD14 were determined by reverse-transcriptase polymerase chain reaction (RT-PCR). Kupffer cells were isolated from the liver by Percoll gradient centrifugation, and were then cultured to measure TNF-alpha production.RESULTS: The serum and liver levels of TNF-a in the CDAA-fecl rats increased significantly as compared with the control group, as did the immunohistochemical values and gene expressions of TNF-a, TLR4, and CD14 with the progression of steatohepatitis. TNF-a production from the isolated Kupffer cells of the CDAA-fed rats was elevated by lipopolysaccharide stimulation.CONCLUSION: The expressions of TNF-alpha, TLR4, and CD14 increased in the NASH model, suggesting that TLR4 and CD14-mediated endotoxin liver damage may also occur in NASH. (C) 2008 The WJG Press. All rights reserved.