摘要
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.
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.
基金
This project was supported by grants from National Science Foundation of China Advanced Program (No. 81030007)
National Science Foundation of China for Young Scholar (No.81100308/H0318)