title: 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.
abstract: As a part of the defense mechanism of the host to viral infection, interferons induce the transcription of several genes. These interferon-inducible genes contribute to the eradication of the viruses. Whereas some studies suggested the participation of a dsRNA-dependent protein kinase in the host reaction to hepatitis C virus infection, the involvement of other interferon-inducible genes has not been evaluated. Furthermore, there has been no analysis on the expression profile of multiple interferon-inducible genes. The aim of this study was to clarify the hepatic mRNA expression profile of interferon-inducible genes with a special concern to chronic hepatitis C. A total of 76 liver biopsy samples (28 with chronic hepatitis C, 10 with chronic hepatitis B, 9 with alcoholic liver disease, 14 with autoimmune hepatitis, 10 with primary biliary cirrhosis, and 5 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 synthetase (2,5-AS), latent cellular endoribonuclease (RNase L), RNase L inhibitor, and MxA. As a result, PKR mRNA was significantly overexpressed in the liver of chronic hepatitis C compared with those of other etiologies (P =.0178), 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 expressions 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 mechanism characteristically.
authors.affiliation: Second Department of Internal Medicine, Tokyo, Japan.
authors.forename: S H
authors.initials: SH
authors.lastname: Yu
authors.forename: K
authors.initials: K
authors.lastname: Nagayama
authors.forename: N
authors.initials: N
authors.lastname: Enomoto
authors.forename: N
authors.initials: N
authors.lastname: Izumi
authors.forename: F
authors.initials: F
authors.lastname: Marumo
authors.forename: C
authors.initials: C
authors.lastname: Sato
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D018833:Chaperonins; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D012330:RNA, Double-Stranded / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D013489:Suppression, Genetic; D014777:Virus Diseases / Q000517:prevention & control*; D019892:eIF-2 Kinase / Q000235:genetics
chemical_list: C501917:ABCE1 protein, human; D018528:ATP-Binding Cassette Transporters; D000998:Antiviral Agents; D011506:Proteins; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D007372:Interferons; D011494:Protein Kinases; D019892:eIF-2 Kinase; D018833:Chaperonins