Shu Wu1,2, Jinpiao Lin1,2, Ya Fu1,2, Qishui Ou1,2. 1. Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China. 2. First Clinical College, Fujian Medical University, Fuzhou, China.
Abstract
BACKGROUND: Interferon (IFN)-α is widely used for the treatment of chronic hepatitis B (CHB) infection due to the high rate of hepatitis B surface antigen (HBsAg) seroconversion. However, IFN-α treatment has a number of side effects. Thus, identification of molecular biomarkers to predict IFN-α therapeutic effect would be useful in the clinic. In this study, we aimed to investigate the role of retinoic acid-inducible gene-I (RIG-I) in prediction of IFN-α curative effect of CHB patients. METHODS: A total of 65 CHB patients treated with pegylated IFN-α weekly for 48 weeks were enrolled. Real-time PCR was performed for detection of RIG-I and IFN-stimulated gene (ISG) expression. In vitro, the HepG2 cells were transfected with siRNA and levels of RIG-I and anti-HBV proteins were detected by western blot. The P-values were calculated in SPSS 18.0. The statistical significance level was accepted as P<0.05. RESULTS: In this study, we found RIG-I expression in peripheral blood mononuclear cells was higher in responder than non-responder CHB patients treated with IFN-α therapy. In HBV-transfected HepG2 and Huh7 cells, RIG-I enhanced IFN-α response by promoting anti-HBV protein expression such as double-stranded RNA-dependent protein kinase (PKR), oligoadenylate synthetase (OAS), adenosine deaminase (ADAR1) and Mx protein. Knocking down of RIG-I could downregulate the expression of these proteins. Inhibited RIG-I expression by RIG-I siRNA deceased STAT1 phosphorylation. CONCLUSIONS: Our results revealed RIG-I enhanced IFN-α response by promoting antiviral protein expression via the STAT1 pathway. RIG-I may be a new predictive factor for prediction of IFN-α efficacy in CHB patients.
BACKGROUND: Interferon (IFN)-α is widely used for the treatment of chronic hepatitis B (CHB) infection due to the high rate of hepatitis B surface antigen (HBsAg) seroconversion. However, IFN-α treatment has a number of side effects. Thus, identification of molecular biomarkers to predict IFN-α therapeutic effect would be useful in the clinic. In this study, we aimed to investigate the role of retinoic acid-inducible gene-I (RIG-I) in prediction of IFN-α curative effect of CHB patients. METHODS: A total of 65 CHB patients treated with pegylated IFN-α weekly for 48 weeks were enrolled. Real-time PCR was performed for detection of RIG-I and IFN-stimulated gene (ISG) expression. In vitro, the HepG2 cells were transfected with siRNA and levels of RIG-I and anti-HBV proteins were detected by western blot. The P-values were calculated in SPSS 18.0. The statistical significance level was accepted as P<0.05. RESULTS: In this study, we found RIG-I expression in peripheral blood mononuclear cells was higher in responder than non-responder CHB patients treated with IFN-α therapy. In HBV-transfected HepG2 and Huh7 cells, RIG-I enhanced IFN-α response by promoting anti-HBV protein expression such as double-stranded RNA-dependent protein kinase (PKR), oligoadenylate synthetase (OAS), adenosine deaminase (ADAR1) and Mx protein. Knocking down of RIG-I could downregulate the expression of these proteins. Inhibited RIG-I expression by RIG-I siRNA deceased STAT1 phosphorylation. CONCLUSIONS: Our results revealed RIG-I enhanced IFN-α response by promoting antiviral protein expression via the STAT1 pathway. RIG-I may be a new predictive factor for prediction of IFN-α efficacy in CHB patients.