Zhu Lin, Chen Tao, Lu Yulei, Wu Di, Luo Xiaoping, Ning Qin
Department and Institute of Infectious Diseases, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Huazhong Univ Sci Technolog Med Sci. 2012 Aug;32(4):552-556. doi: 10.1007/s11596-012-0095-6. Epub 2012 Aug 11.
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.
最近研究表明，Th17细胞和白细胞介素-17（IL-17）在乙型肝炎免疫介导的肝损伤中起关键作用，然而它们在急性肝衰竭中的功能尚未完全阐明。在本研究中，我们主要探究了IL-17在小鼠肝炎病毒3型（MHV-3）诱导的急性肝衰竭发展过程中的作用。在MHV-3诱导的小鼠暴发性肝炎模型中，采用定量实时聚合酶链反应定量检测肝组织中IL-17信使核糖核酸（mRNA）水平，采用酶联免疫吸附测定法（ELISA）检测肝组织和血清中细胞因子IL-17水平。采用流式细胞术检测CD4(+)T细胞和CD8(+)T细胞上IL-17的表达水平。研究IL-17水平与肝损伤之间的相关性。还通过细胞内染色研究了与Th17相关的细胞因子。我们的结果显示，感染MHV-3的BALB/cJ小鼠肝脏和血清中IL-17表达显著升高。此外，一项时间进程研究表明，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细胞百分比均显著增加，并在感染后72小时达到峰值。肝组织或血清中IL-17浓度分别与由丙氨酸转氨酶（ALT）水平定义的肝损伤严重程度密切相关。感染后72小时，与Th17相关的细胞因子IL-6、IL-21和IL-22也显著增加。得出的结论是，IL-17可能参与了MHV-3诱导的急性肝衰竭的发病机制。
