title: Interferon-beta reduces the mouse liver fibrosis induced by repeated administration of concanavalin A via the direct and indirect effects.
abstract: Type I interferons (IFNs), IFN-alpha and IFN-beta, are widely used for treating chronic hepatitis C. Although retrospective studies have suggested that type I IFNs have direct antifibrotic effects, little is known about these mechanisms. The present study was designed to clarify the preventive mechanisms of type I IFNs in the progression of fibrosis for the establishment of a more effective therapy. A murine fibrosis model comprising immunological reactions was induced by the administration of concanavalin A (0.3 mg/body) into mice once a week for 4 weeks. Liver injury and the degree of fibrosis were determined by measuring the serum alanine aminotransferase activities and liver hydroxyproline contents with or without IFN-beta pretreatment. IFN-beta suppressed the hepatocellular injury and increased the hydroxyproline content induced by repeated concanavalin A injections, but had no effect on established fibrosis. Furthermore, IFN-beta reduced the expressions of transforming growth factor-beta, basic fibroblast growth factor, collagen type I A2 and tissue inhibitor of metalloproteinase 1 messenger RNAs, which are related to the progression of liver fibrosis. The IFN-beta reduced the liver injury and fibrosis induced by immunological reactions. These data suggest that type I IFNs suppress the progression of cirrhosis through inhibition of repeated hepatocellular injury and/or factors that promote the liver fibrosis induced by hepatitis virus infection.
authors.affiliation: Pharmaceutical Research Laboratory, Toray Industries Inc., Kanagawa, Japan. Junichi_Tanabe@nts.toray.co.jp
authors.forename: Junichi
authors.initials: J
authors.lastname: Tanabe
authors.forename: Akiko
authors.initials: A
authors.lastname: Izawa
authors.forename: Natsumi
authors.initials: N
authors.lastname: Takemi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyauchi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Torii
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tsuchiyama
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Suzuki
authors.forename: Saburo
authors.initials: S
authors.lastname: Sone
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ando
mesh_terms: D000818:Animals; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D024042:Collagen Type I; D003208:Concanavalin A; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D006487:Hemostasis / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D007370:Interferon Type I / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D024042:Collagen Type I; D016207:Cytokines; D006133:Growth Substances; D007370:Interferon Type I; D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D003208:Concanavalin A; D003094:Collagen; D006909:Hydroxyproline