Antifibrogenic Effect of IFN-α2b on Hepatic Stellate Cell Activation by Human Hepatocytes

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Abstract
Liver fibrosis commonly occurs in patients with hepatitis C virus (HCV) infection as a consequence of the chronic liver damage, thus leading to the development of liver cirrhosis. When hepatic stellate cells (HSCs) become active, they play an essential role in liver fibrogenesis. In this study, interleukin-1β (IL-1β) and tumornecrosis factor-α (TNF-α), commonly elevated in chronic C hepatitis, stimulate the production of matrix metalloprotease-9 (MMP-9) by human hepatocytes at a transcriptional and translational level, but the addition of recombinant interferon-α2b (rIFN-α2b) hampers this effect. Furthermore, a human HSC line is activated in vitro by incubation with human MMP-9 in the presence of collagen I, and this effect is blocked by the MMP inhibitor BB94. A similar activation was observed when incubating HSCs with conditioned medium of hepatocytes previously stimulated with IL-1β and TNF-α but not when using conditioned medium of hepatocytes costimulated with IL-1β or TNF-α together with rIFN-α2b. In conclusion, our results show that hepatocytes stimulated by inflammatory cytokines participate in the activation of HSCs via MMP-9 production and that antiviral therapy modulates such activation.