Transforming growth factor beta in hepatitis C virus infection: In vivo and in vitro findings

Abstract

Background: Hepatitis C virus (HCV) is a leading cause of chronic liver disease (CLD) worldwide. The chronicity is a result of viral persistence and the ability of the virus to escape from the immune mechanisms of the host. Transforming growth factor (TGF)-β is a cytokine thought to be responsible for viral persistence and liver fibrogenesis. Methods: The present study examined the levels of TGF-β messenger (m)RNA by reverse transcription polymerase chain reaction (RT-PCR) in 35 liver biopsies and HCV-transfected HepG2 cells. Results: Transforming growth factor-β mRNA was detected in nine liver biopsies from patients with chronic HCV infection, but was not detected in patients with non-HCV-related CLD or controls. On quantitation by semiquantitative PCR, TGF−β mRNA levels ranged from 10^−4.75 to 10^−12.8 amol (10^−7.46 ± 3.771) in liver biopsies of HCV-related CLD. No significant difference in TGF-β receptor levels was observed by RT-PCR in HCV- or non-HCV-related CLD by immunohistochemistry. To correlate these findings with in vitro experiments, levels of TGF-β mRNA and its receptors were determined by RT-PCR in HepG2 cells transfected with HCV and hepatitis B virus (HBV) constructs, using mock-transfected cells as control. The TGF-β protein levels were quantitated in these cell supernatants by enzyme immunoassay. The TGF-β mRNA and protein levels were two logs and approximately 30 times higher in HCV-transfected HepG2 cells than in HBV- and mock-transfected cells, respectively. The TGF-β receptors in HepG2 cells were also downregulated in HCV-transfected cells as compared with mock-transfected cells. Conclusion: These observations suggest upregulation of TGF-β in HCV infection and a probable role for TGF-β in the pathogenesis of HCV-related CLD.