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.
Lee
Sang Hun
SH
School of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea.
Park
Sung Gyoo
SG
Lim
Seung Oe
SO
Jung
Guhung
G
D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D008233:Lymphotoxin-alpha / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology*; D014162:Transfection; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
D008233:Lymphotoxin-alpha; D016328:NF-kappa B; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein