Intrahepatic mRNA expression of interferon-inducible antiviral genes in liver diseases: dsRNA-dependent protein kinase overexpression and RNase L inhibitor suppression in chronic hepatitis C

As a part of the defense mechanism of the host to viral infection, interfer ons induce the transcription of several genes. These interferon-inducible g enes contribute to the eradication of the viruses. Whereas some studies sug gested the participation of a dsRNA-dependent protein kinase in the host re action to hepatitis C virus infection, the involvement of other interferon- inducible genes has not been evaluated. Furthermore, there has been no anal ysis on the expression profile of multiple interferon-inducible genes. The aim of this study was to clarify the hepatic mRNA expression profile of int erferon-inducible genes with a special concern to chronic hepatitis C. A to tal of 76 liver biopsy samples (28 with chronic hepatitis C, 10 with chroni c hepatitis B, 9 with alcoholic liver disease, 14 with autoimmune hepatitis , 10 with primary biliary cirrhosis, and S of normal liver) were enrolled. The expression of the following genes was quantified by competitive reverse transcription-polymerase chain reaction and was compared according to the etiology; dsRNA-dependent protein kinase (PKR), 2',5'-oligoadenylate synthe tase (2,5-AS), latent cellular endoribonuclease (RNase L), RNase L inhibito r, and MxA. As a result, PKR mRNA was significantly overexpressed in the li ver of chronic hepatitis C compared with those of other etiologies (P = .01 78), and it correlated significantly with serum alanine transaminase values (r = .51, P = .0054). Also, the expression of the RNase L inhibitor showed a significant reduction in chronic hepatitis C (P = .0184), The expression s of 2,5-AS, RNase L, and MxA were not different significantly irrespective to the etiology. In conclusion, hepatic overexpression of PKR and reduced expression of RNase L inhibitor seem to contribute to the anti-HCV mechanis m characteristically.