INDUCIBLE NITRIC-OXIDE SYNTHASE EXPRESSION IN CHRONIC VIRAL-HEPATITIS

Increased nitric oxide (NO) production may contribute to the pathologi cal changes featuring in some inflammatory diseases, but the role of N O in chronic viral hepatitis is still unknown, We compared the inducib le NO synthase (NOS2) expression in the liver of patients with chronic viral hepatitis with that of both nonviral liver disease and histolog ically normal liver, NOS2 expression was assessed by immunohistochemic al and in situ hybridization studies of liver biopsy sections, An inte nse hepatocellular NOS2 reactivity was detected in chronic viral hepat itis, whereas it was weakly or not observed in nonviral liver disease or normal liver, respectively, In addition, we determined whether the hepatitis B virus (HBV) might regulate the synthesis of this enzyme. N OS2 mRNA and protein levels as well as enzyme activity were assessed i n cytokine-stimulated HBV-transfected and untransfected hepatoma cells , Transfection with either HBV genome or HBV X gene resulted in induct ion of NOS2 mRNA expression, and the maximal induction of this transcr ipt and NO production was observed in cytokine-stimulated HBV-transfec ted cells, These results indicate that hepatotropic viral infections a re able to upregulate the NOS2 gene expression in human hepatocytes, s uggesting that NO may mediate important pathogenic events in the cours e of chronic viral hepatitis.