Inhibitory effect of human interferon-beta-1a on activated rat and human hepatic stellate cells.

Background and Aims: Hepatic stellate cells (HSC) are the primary cell type mediating hepatic fibrosis. Although known for its antiviral effects, the inhibitory effects of interferon-beta (IFN-beta) on HSC treatment have not yet been established. Methods: Both human and rat activated HSC cell lines were incubated with increasing concentrations of recombinant human IFN-beta 1a (rhIFN-beta 1a) for 24, 48 or 72 h. The effects of rhIFN-beta 1a on alpha-smooth muscle actin (alpha-SMA), collagen types I and III, transforming growth factor-beta 1 (TGF-beta 1), platelet-derived growth factor-BB (PDGF-BB), and mothers against decapentaplegic homolog (Smad4, Smad7) expression in HSC were examined using Western blotting and immunocytochemistry. Proliferation of HSC was evaluated via bromodeoxyuridine assay. Results: rhIFN-beta 1a treatment had a dose-dependent, inhibitory effect on alpha-SMA and collagen type I protein expression. In addition, rhIFN-beta 1a decreased the expression of collagen type III, TGF-beta 1, PDGF-BB and Smad4 protein expression in HSC compared with untreated cells. We also observed increased Smad7 protein expression and decreased proliferation in rhIFN-beta 1a-treated HSC. Conclusions: Our data suggest that rhIFN-beta 1a treatment decreased alpha-SMA and collagen expression and inhibited the activation of HSC through the inhibition of the TGF-beta and PDGF pathways.