Hepatocyte growth factor upregulates interferon signaling in human hepatocytes: Possible implications for interferon therapy after liver transplantation

Background/Aim: Although a recurrent hepatitis C virus (HCV) infection is the leading cause of graft loss in liver transplant recipients, the optimal timing to begin interferon (IFN) therapy after LTx is still unknown. The purpose of this study is to analyze the relationships, between signaling by PEGylated IFN in human hepatocytes, with regard to hepatocyte proliferation, and immunosuppressive drugs in vitro. Methods: Experiment 1 - Normal human hepatocytes (NhHeps) were cultured with/without recombinant human hepatocyte growth factor (r-hHGF) for 48 h, and then treated with 100 IU/mL IFN at the indicated time. The expressions of double-stranded RNA-dependent protein kinase (PKR) and IFN- α-induced antiviral protein were analyzed using Western blotting for the extracted lysates from these cells. Experiment 2 - The NhHeps were cultured in 10% medium containing varying concentrations of tacrolims (Tac), cyclosporine A (CyA), and methylprednisolone (PLS), and the cells were treated with 100 IU/mL IFN at the indicated time. Subsequently, the density of PKR was examined. Results: The expression of PKR was enhanced by HGF. PKR induction by IFN was suppressed by Tac > CyA > PLS. Conclusion: Hepatocyte proliferation induced by HGF did not interfere with the signaling by IFN. The presence of immunosuppressive drugs was therefore found to negatively affect IFN signaling