Altered Expression of Fas (APO-1, CD95) and Fas Ligand in the Liver of Mice Infected with Schistosoma Japonicum and Schistosoma Mansoni: Implications for Liver Carcinogenesis

Abstract

Epidemiological studies have associated infection with Schistosoma japonicum and S. mansoni with increased ‍risk of cancers of the liver and colon, although the mechanism of carcinogenesis remains unestablished. The livers of ‍mice experimentally infected with S. japonicum or S. mansoni were analysed for expression of Fas (CD95/APO-1) ‍and Fas ligand immunohistochemically and for apoptotic cell death by the TUNEL method. Fas expression was ‍significantly decreased in hepatocytes around the inflammatory area of egg granulomas; this decrease was most ‍prominent during the chronic phase of infection. Fas ligand was expressed in hepatocytes inside and outside ‍granulomas, especially from mice at the early stage of infection, but not in hepatocytes from uninfected mice. Abnormal ‍proliferation and Fas ligand expression were also observed in capillary bile ducts inside egg granulomas. Apoptotic ‍cell death of inflammatory cells and, less frequently, of hepatocytes was found both inside and around granulomas. ‍The rate of apoptotic cell death was high during the early stage of infection with S. mansoni, but decreased during ‍the chronic phase of infection. Our results suggest that schistosome infection causes alterations of the Fas-Fas ‍ligand system, one of the major apoptotic pathways, in mouse liver.