The Effect of SB431542, TGF-β Receptor Inhibitor, on HCV Replication in PBMCs of Patients with Chronic Hepatitis

Background and Aims: TGF-β is an effective cytokine in the viral replication cycle, which is also highly relevant to the pathogenesis of some viral infections. TGF-β induction by viral proteins is one of the ways to escape the virus from the immune system by inhibiting interferon signaling and other immune system factors.  In recent years, the role of TGF-β and its inhibitory signaling has been confirmed in clinical trials. In this study, using SB431542, a TGF-β type I activin receptor like kinase inhibitor, the effect of TGF-β reduction on IFN expression and antiviral activity in PBMCs of patients with chronic hepatitis C was investigated. Materials and Methods: PBMCs from 10 patients with chronic hepatitis and 5 healthy individuals were isolated with Ficoll solution and cultured in the presence of different concentrations of sb431542. RNA was extracted at different time points of culture, with Qiazol lysis reagent and cDNA was synthesized with commercial kits. The relative expression levels of TGF-β, IFN-α and HCV Core mRNA were determined using with REAL TIME PCR. The expression level of TGF-β protein was also measured in supernatant of cultured cells by ELISA method. Results: The inhibitory effect of different concentrations of SB431542 at various time point showed that it peaks 48h after treatment and the maximum increase of IFN-α expression and significant antiviral effects reached 72 h after treatment. Conclusions: The effects of TGF-β on IFNs may be correlated with inverse ratio depending on the level and duration of expression, which indicates the regulatory role of these proteins in the immune system against the viruses. TGF inhibitory drugs can augment immune system against the viruses.