Contribution of IL-17 to mouse hepatitis virus strain 3-induced acute liver failure
Contribution of IL-17 to mouse hepatitis virus strain 3-induced acute liver failure
复制标题
DOI：
10.1007/s11596-012-0095-6
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Lin Zhu 朱 琳;Tao Chen 陈 韬;Yulei Lu 陆玉蕾;Di Wu 吴 迪;Xiao-ping Luo 罗小平;Qin Ning 宁 琴
中科院分区：
文献类型：
--
作者：
Lin Zhu 朱 琳;Tao Chen 陈 韬;Yulei Lu 陆玉蕾;Di Wu 吴 迪;Xiao-ping Luo 罗小平;Qin Ning 宁 琴
最近，Th17细胞和IL-17已被证明在乙型肝炎免疫介导的肝损伤中发挥关键作用，但它们在急性肝衰竭中的功能尚未得到很好的阐明。在本研究中，我们主要研究了 IL-17 在小鼠肝炎病毒 3 株 (MHV-3) 诱导的急性肝衰竭发展中的作用。采用实时定量聚合酶链反应定量肝组织中IL-17 mRNA水平，并在MHV-3诱导的小鼠暴发性肝炎模型中采用ELISA测定肝组织和血清中细胞因子IL-17水平。使用流式细胞术测定CD4+T和CD8+T细胞上IL-17的表达水平。研究IL-17水平与肝损伤的相关性。还通过细胞内染色研究了 Th17 相关细胞因子。我们的结果表明，感染 MHV-3 的 BALB/cJ 小鼠的肝脏和血清中 IL-17 表达显着升高。此外，一项时间过程研究表明，从感染后48小时开始，肝脏中产生IL-17的CD4+T细胞和产生IL-17的CD8+T细胞的百分比显着增加，并在感染后72小时达到峰值。肝脏或血清 IL-17 浓度与 ALT 水平定义的肝损伤严重程度之间存在密切相关。感染后 72 小时，Th17 相关细胞因子 IL-6、IL-21 和 IL-22 也显着增加。结论是IL-17可能参与MHV-3诱导的急性肝衰竭的发病机制。
Recently, the Th17 cells and IL-17 have been shown to play a critical role in the immune-mediated liver injury in hepatitis B, while their functions in acute liver failure have not been well elucidated yet. In this study, we primarily investigated the role of IL-17 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure. IL-17 mRNA levels in liver tissue were quantified by using quantitative real-time polymerase chain reaction, and cytokine IL-17 levels in liver tissue and serum were determined by using ELISA in MHV-3-induced murine fulminant hepatitis model. The IL-17 expression levels on CD4+T and CD8+T cells were determined by using flow cytometry. The correlation between IL-17 level and liver injury was studied. Th17 associated cytokines were also investigated by intracellular staining. Our results showed that the IL-17 expression was significantly elevated in the liver and serum of BALB/cJ mice infected with MHV-3. Moreover, a time course study showed that the percentage of both IL-17-producing CD4+T cells and IL-17-producing CD8+T cells was increased remarkably in the liver starting from 48 h and peaked at 72 h post-infection. There was a close correlation between hepatic or serum IL-17 concentration and the severity of liver injury defined by ALT level, respectively. Th17 associated cytokines, IL-6, IL-21 and IL-22, were also increased significantly at 72 h post-infection. It was concluded that IL-17 may contribute to the pathogenesis of MHV-3-induced acute liver failure.