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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
Author(s) -
Yu ShinHan,
Nagayama Kazuyoshi,
Enomoto Nobuyuki,
Izumi Namiki,
Marumo Fumiaki,
Sato Chifumi
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2000.19287
Subject(s) - interferon , protein kinase r , biology , virology , microbiology and biotechnology , liver biopsy , messenger rna , gene , protein kinase a , kinase , medicine , biopsy , mitogen activated protein kinase kinase , biochemistry
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.