Interaction of interferon-alpha with interleukin-1 beta or tumor necrosis factor-alpha on hepatitis B virus enhancer activity.
The interaction of IFN-alpha with IL-1 beta or TNF-alpha on hepatitis B surface antigen (HBsAg) expression was analysed in hepatitis B virus (HBV)-DNA integrated PLC/PRF/5 and non-integrated HuH-7 human hepatoma cells. Secretion of HBsAg in PLC/PRF/5 cells was reduced by IFN-alpha, IL-1 beta or TNF-alpha, and synergistically depressed when IFN-alpha was used in combination with IL-1 beta or TNF-alpha. By Northern blot analysis, the levels of HBsAg mRNA were suppressed by IFN-alpha in combination with IL-1 beta or TNF-alpha. In the chloramphenicol acetyltransferase plasmid transfection assay, IFN-alpha in combination with IL-1 beta or TNF-alpha caused a much greater suppression of HBV enhancer activity than IFN-alpha, IL-1 beta or TNF-alpha alone in both hepatoma cells. These findings suggest that the interaction of IFN-alpha with IL-1 beta or TNF-alpha synergistically represses HBV enhancer activity, resulting in depressed expression of HBsAg.
Hamasaki
K
K
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Nakata
K
K
Nakao
K
K
Mitsuoka
S
S
Tsutsumi
T
T
Kato
Y
Y
Shima
M
M
Ishii
N
N
Tamaoki
T
T
Nagataki
S
S
D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000382:microbiology; D015500:Chloramphenicol O-Acetyltransferase; D016207:Cytokines / Q000494:pharmacology*; D006513:Hepatitis B e Antigens / Q000187:drug effects / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000382:microbiology; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D016207:Cytokines; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D007375:Interleukin-1; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D015500:Chloramphenicol O-Acetyltransferase