Association of CX3CL1 and CX3CR1 Expression with Liver Fibrosis in a Mouse Model of Schistosomiasis

摘要

Immunopathological mechanisms of schistosomiasis,a debilitating parasitic disease,are still unclear.In this study,we investigated the involvement of CX3C chemokine ligand 1(CX3CL1)and its sole receptor CX3CR1 in the development of liver fibrosis in schistosomiasis.The animal model of schistosomiasis was established by infection of C57BL/6 mice with Schistosoma japonicum cercariae;mice injected with carbon tetrachloride(CCl4)were used as positive control of liver injury.After 4 and 8 weeks,the degree of liver lesions was assessed by hematoxylin and eosin staining,serum levels of hyaluronic acid(HA)were analyzed by a chemiluminescence immunoassay,liver fibrosis was evaluated by immunohistochemistry analysis ofα-smooth muscle actin(α-SMA)expression,and CX3CL1 and CX3CR1 expression in the liver was measured by immunohistochemistry and real-time PCR.The results showed that at 8 weeks after Schistosoma infection,serum HA levels were increased andα-SMA-expressing cells appeared in the liver,indicating fibrogenesis.CX3CL1-and CX3CR1-positive cells were observed in the outer layer of granulomas formed around Schistosoma eggs in liver tissues,which was consistent with the significant upregulation of hepatic CX3CL1 and CX3CR1 mRNA expression at 4 and 8 weeks post-infection.Furthermore,correlation analysis revealed positive association between CX3CL1 and CX3CR1 expression and serum HA levels at 8 weeks post-infection,indicating a link between fibrogenesis and the CX3CL1/CX3CR1 axis in schistosomiasis.In conclusion,our data suggest the involvement of CX3CL1 and CX3CR1 in the progression of liver fibrosis caused by Schistosoma infection.