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-β) 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-β1a (rhIFN-β1a) for 24, 48 or 72 h. The effects of rhIFN-β1a on α-smooth muscle actin (α-SMA), collagen types I and III, transforming growth factor-β1 (TGF-β1), 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-β1a treatment had a dose-dependent, inhibitory effect on α-SMA and collagen type I protein expression. In addition, rhIFN-β1a decreased the expression of collagen type III, TGF-β1, PDGF-BB and Smad4 protein expression in HSC compared with untreated cells. We also observed increased Smad7 protein expression and decreased proliferation in rhIFN-β1a-treated HSC.

CONCLUSIONS: Our data suggest that rhIFN-β1a treatment decreased α-SMA and collagen expression and inhibited the activation of HSC through the inhibition of the TGF-β and PDGF pathways.