The hepatitis B virus X protein up-regulates lymphotoxin α expression in hepatocytes

Hepatitis B virus X protein (HBx) is involved in intrahepatic inflammatory processes by inducing several pro-inflammatory cytokines. It has been suggested that these inflammatory processes play an important role in causing hepatocarcinogenesis. In this study, we investigated the role of HBx in the expression of lymphotoxin α (LTα) in hepatoma cells such as Huh-7 and Chang. Our experiments showed that (i) transient HBx expression in Huh-7 cells up-regulated LTα mRNA expression; (ii) this up-regulation was predominantly affected by HBx-induced nuclear factor-κB (NF-κB) activation. In addition, the HBx-induced NF-κB activation was decreased by the treatment of LTα neutralizing antibodies in a dose-dependent manner. We conclude that HBx up-regulates LTα expression at the transcriptional level through an NF-κB-dependent mechanism and, therefore, the up-regulated LTα may be secreted and involved in the HBx-induced NF-κB activation.