Transcription Factor MafB Suppresses Type I Interferon Production by CD14 + Monocytes in Patients With Chronic Hepatitis C.

Transcription factor MafB regulates differentiation and activity of monocytes/macrophage and is associated with the development of atherosclerosis and cancers. However, the role of MafB in modulation of CD14(+) monocytes in chronic viral hepatitis was not fully elucidated. Thus, the aim of current study was to investigate the immunoregulatory function of MafB to type I interferon (IFN) secretion by CD14(+) monocytes and its contribution to pathogenesis of chronic hepatitis C virus (HCV) infection. A total of 29 chronic hepatitis C patients and 21 healthy individuals were enrolled. Serum IFN-alpha 1 and IFN-beta was measured by ELISA, while MafB mRNA and protein expression were assessed by real-time PCR and Western blot. MafB siRNA or MafB expression plasmid was transfected into purified CD14(+) monocytes to suppress or increase MafB expression. The function of MafB siRNA transfected CD14(+) monocytes to HCV in cell culture (HCVcc)-infected Huh7.5 cells or CD4(+) T cells was also investigated in direct and indirect contact co-culture system. Serum IFN-alpha 1 and IFN-beta was robustly reduced in chronic hepatitis C patients. By contrast, MafB was notably elevated in chronic hepatitis C patients and negatively correlated with serum IFN-alpha 1. Overexpression of MafB reduced the IFN-alpha 1 production by CD14(+) monocytes from healthy individuals. However, MafB inhibition elevated IFN-alpha 1 secretion by CD14(+) monocytes and interferon regulatory factor 3 phosphorylation in chronic hepatitis C. MafB inhibition also promoted CD14(+) monocytes-induced viral clearance in HCVcc-infected Huh7.5 cells by up-regulation of IFN-alpha 1 and IFN-beta without increasingly destroying hepatocytes, however, did not affect CD14(+) monocytes-induced CD4(+) T cells differentiation in chronic hepatitis C patients. The current data revealed that overexpression of MafB in chronic hepatitis C patients might suppress type I IFN production by CD14(+) monocytes, leading to the viral persistence. MafB might be a potential therapeutic target for treatment of chronic hepatitis C.