IFI16 induces inflammation in Hepatitis B Virus-Associated Glomerulonephritis by Regulating the Caspase-1 /IL-1ß pathway
Abstract Aims & backgroundIFI16 plays an important role in innate immunity against invasive microbial infection by sensing double-stranded DNA viruses due to caspase-1-dependent inflammasome activation and subsequent maturation and secretion of IL-1β. However, the role of IFI16 in regulating the immune response to viruses in Hepatitis B Virus-Associated Glomerulonephritis(HBV-GN), especially in sensing the hepatitis B virus (HBV), has not been determined. In this study,, we investigated the inflammatory role of IFI16 in HBV-GN.MethodsA total of 75 kidney tissues including 50 HBV-GN and 25 chronic glomerulonephritis (CCN) were collected to determine expression of IFI16, Caspase-1, and IL-1𝛽 by immunohistochemistry (IHC), and then the correlation between them was analyzed. In vitro, the overexpression or knockdown of IFI16 in regulating the immune response to HBV infection in the human glomerular mesangial (HGM) cell line and HEK-293T cell line. Quantitative Real-time PCR and western blotting were used to determine the expression of IFI16, Caspase-1 and IL-1β. The role effect of IFI16 in vivo was further investigated.ResultsIFI16 expression in HBV-GN biopsies (80.0%) was significantly higher than in CGN (24.0%) and was positively correlated with caspase-1 and IL-1𝛽 expression in HBV-GN. In vitro, over expression of IFI16 increased caspase-1 and IL-1𝛽 expression in HBV-infected HGM and HEK-293T cell lines, whereas knockdown of IFI16 mRNA by siRNA resulted in downregulation of the caspase-1 and IL-1𝛽 expression in both cell lines.ConclusionsThe elevation of IFI16 during HBV infection or replication may contribute to renal damage due to inflammation, thus providing a putative therapeutic target and a new avenue for studying the pathogenesis of HBV-GN.