title: 9-cis retinoic acid enhances the antiviral effect of interferon on hepatitis C virus replication through increased expression of type I interferon receptor.
abstract: The concentration of type I interferon receptor (IFN-Rc) in the liver is a crucial factor in determining the efficacy of interferon (IFN) therapy in patients with chronic hepatitis C. Retinoic acids (RAs) can enhance the expression of type I IFN-Rc expression. The aim of this study was to investigate whether RAs increase the anti-hepatitis C virus (HCV) effect of IFN through an increase in IFN-Rc. The hepatocellular carcinoma cell line HuH-7 was treated with 10(-7) mol/L all-trans RA (ATRA) and 9-cis RA (9-CRA). Expression of type I IFN-Rc was investigated at both the mRNA and protein levels with the use of real-time quantitative polymerase chain reaction and flow cytometry, respectively. We investigated the anti-HCV effect, using in vitro HCV transfection, by monitoring the level of HCV RNA in the culture medium. ATRA and 9-CRA enhanced the expression of type I IFN-Rc at both the mRNA and protein levels. After IFN-alpha treatment, the activity of 2,5'-oligoadenylate synthetase was enhanced by RAs, and this enhancement was abolished when blocking antibodies had previously been bound to the surface receptors. IFN treatment decreased the concentration of HCV RNA, and this effect was enhanced by treatment with RAs. Our findings suggest that RAs enhance the anti-HCV replication effect of IFN-alpha through up-regulation of type I IFN-Rc in HuH-7 cells.
authors.affiliation: Second Department of Internal Medicine, Shimane Medical University, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hamamoto
authors.forename: Ryo
authors.initials: R
authors.lastname: Fukuda
authors.forename: Norihisa
authors.initials: N
authors.lastname: Ishimura
authors.forename: Mohammed Azharul Karim
authors.initials: MA
authors.lastname: Rumi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kazumori
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Uchida
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kadowaki
authors.forename: Shunji
authors.initials: S
authors.lastname: Ishihara
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000077556:Alitretinoin; D000906:Antibodies / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D008113:Liver Neoplasms; D008565:Membrane Proteins; D012367:RNA, Viral / Q000032:analysis; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000906:Antibodies; D000998:Antiviral Agents; D016898:Interferon-alpha; D008565:Membrane Proteins; D012367:RNA, Viral; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D000077556:Alitretinoin; D014212:Tretinoin; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase