Jun-Ichi Tanabe

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

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.

An infectious and selectable full-length replicon system with hepatitis C virus JFH-1 strain.

Aim:  The hepatitis C virus (HCV) strain JFH‐1 was cloned from a patient with fulminant hepatitis. A JFH‐1 subgenomic replicon and full‐length JFH‐1 RNA efficiently replicate in cultured cells. In this study, an infectious, selectable HCV replicon containing full‐length JFH‐1 cDNA was constructed.

Inflammatory cytokines modulate chemokine production patterns of HepG2 cells toward initially inclined direction

Aim:  Human hepatocytes are known to express an array of inflammatory cytokines and chemokines. In this study, we examined the potential roles of hepatocytes in regulating immune responses in the liver, by assessing the induction of Th1‐ or Th2‐specific chemokines in HepG2 cells after various inflammatory stimulations.

The combination of type I interferon and ribavirin has an inhibitory effect on mouse hepatitis virus infection

Aim:  To determine the differences in efficacy between therapy using IFN‐β and ribavirin, and using IFN‐α and ribavirin.