The hepatitis B virus X protein up-regulates lymphotoxin alpha 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 alpha (LTalpha) in hepatoma cells such as Huh-7 and Chang. Our experiments showed that (i) transient HBx expression in Huh-7 cells up-regulated LTalpha mRNA expression; (ii) this up-regulation was predominantly affected by HBx-induced nuclear factor-kappaB (NF-kappaB) activation. In addition, the HBx-induced NF-kappaB activation was decreased by the treatment of LTalpha neutralizing antibodies in a dose-dependent manner. We conclude that HBx up-regulates LTalpha expression at the transcriptional level through an NF-kappaB-dependent mechanism and, therefore, the up-regulated LTalpha may be secreted and involved in the HBx-induced NF-kappaB activation.