Down-regulation of Toll-like receptor 7 expression in hepatitis-virus–related human hepatocellular carcinoma

Summary Toll-like receptors (TLRs) play a pivotal role in innate immunity, controlling inflammatory responses, and further development of adaptive immunity. Hepatitis virus can establish chronic infection, and the associated inflammatory responses are important determinants of virus-associated liver damage. However, the contributions of the host immune system to chronic presence of virus are not clear in patients with hepatitis virus infection. Chronic inflammatory conditions caused by persistent hepatitis virus infections and interferon (IFN)- γ -related immunopathology are known to be related to carcinogenesis. To gain insight into the role of immune modulation in the pathogenesis of hepatocellular carcinoma (HCC), we studied the expression of TLR7 in cancerous and non-cancerous liver tissue from 87 patients with HCC. Our results showed that TLR7 is significantly down-regulated in neoplastic hepatocytes ( P TLR7 promoter, a hepatocyte-specific regulatory region was found at nucleotides −156 to −98 in the TLR7 promoter. Furthermore, the effects of IFN- γ on TLR7 expression in a hepatoma cell line (HepG2) were investigated in vitro. We demonstrated that IFN- γ significantly decreased TLR7 promoter activity and expression in a dose-dependent manner. We thus propose that hepatitis virus induces down-regulation of TLR7 gene expression through IFN- γ , thereby modulating inflammatory signaling in hepatoma cells.