Interferon‐β reduces the mouse liver fibrosis induced by repeated administration of concanavalin A via the direct and indirect effects

Abstract

Summary Type I interferons (IFNs), IFN‐α and IFN‐β, 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‐β pretreatment. IFN‐β suppressed the hepatocellular injury and increased the hydroxyproline content induced by repeated concanavalin A injections, but had no effect on established fibrosis. Furthermore, IFN‐β reduced the expressions of transforming growth factor‐β, 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‐β 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.

The Effects of Interferon-α2b on Intestinal Flora in Peritoneal Fibrosis

“…In experimental studies, it has been demonstrated that IFN reduces the expression of TGF-f3, as well as basic fibroblast growth factor, which are associated with liver fibrosis (4).…”

The Effects of Interferon α2b on Chemically-Induced Peritoneal Fibrosis and on Peritoneal Tissue MMP-2 and TIMP-2 Levels in Rats

“…8 In experimental studies, IFN reduced the expression of TGF-β and bFGF, both of which are associated with liver fibrosis. 9 The MMPs and their natural inhibitors are involved in the development and continuation of PF. 14,15 It has been demonstrated that MMPs and TIMPs are produced within the peritoneum by peritoneal mesothelial cells, fibroblasts and macrophages, and MMP-2, MMP-3, MMP-9, TIMP-1 and TIMP-2 activities have been measured in peritoneal cell cultures.…”

“…8 The mechanism of the antifibrotic effect is not fully understood, although experimental mouse studies have demonstrated that IFN decreases the expression of TGF-β and basic fibroblast growth factor (bFGF), both of which are associated with hepatic fibrosis. 9 To date, and to the authors' knowledge, there are no studies demonstrating the efficacy of pegylated IFN-α2b in PF. The aim of the present study was to investigate the effect of pegylated IFN-α2b on chlorhexidine gluconate (CH)-induced PF in Wistar rats, and to assess the levels of MMP-2 and TIMP-2 in peritoneal tissue in this experimental animal model.…”

Host Cell Cytokines Induced by Chlamydia pneumoniae Decrease the Expression of Interstitial Collagens and Fibronectin in Fibroblasts

“…These experiments focused on bFGF and IFN-␤ because both mediators have been reported to suppress interstitial collagen expression and are known to be produced by Chlamydia-infected cells (20,34,36,46). Antibodies to bFGF had no effect on the capacity of the conditioned medium to inhibit matrix protein synthesis (Fig.…”