Recombinant HBsAg inhibits LPS-induced COX-2 expression and IL-18 production by interfering with the NFkappaB pathway in a human monocytic cell line, THP-1.
OBJECTIVE
Hepatitis B virus suppresses the human immune-system and HBsAg inhibits the induction of cytokines by LPS in human macrophages, but the mechanisms involved remain unclear. COX-2 and its product, PGE2, play a role in hepatitis B and IL-18 has also been shown to inhibit HBV infection in vivo. We investigated whether rHBsAg affects induction of COX-2 and IL-18 by LPS and, if so, which signal pathways are involved in a human monocytic cell line, THP-1.


METHODS
Cell culture, Western blotting for COX-2, ERK and IKB-alpha, immunofluorescence for HBsAg and NFkappaB protein and ELISA for PGE2, IL-18 and IL-12 were performed.


RESULTS
rHBsAg inhibits LPS-induced COX-2 expression in a time- and dose-dependent manner by blocking the ERK and NFkappaB pathways. LPS-induced IL-18 production was also down-regulated by rHBsAg by interfering mainly with the NFkappaB pathway. PGE2 reversed the inhibition of LPS-induced IL-18 production by rHBsAg. rHBsAg was also found to inhibit the induction of IL-12 by LPS in THP-1 cells.


CONCLUSIONS
These results showed a novel anti-inflammatory property of rHBsAg which involves inhibition of COX-2 and suggested that hepatitis B virus may regulate IFN-gamma production by inhibiting IL-18 and IL-12 production.
Cheng
Jidong
J
Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo 663, Japan. chjd@hyo-med.ac.jp
Imanishi
Hiroyasu
H
Morisaki
Hiroko
H
Liu
Weidong
W
Nakamura
Hideji
H
Morisaki
Takayuki
T
Hada
Toshikazu
T
D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D051546:Cyclooxygenase 2; D015237:Dinoprost / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006514:Hepatitis B Surface Antigens / Q000494:pharmacology*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008565:Membrane Proteins; D009000:Monocytes; D016328:NF-kappa B / Q000187:drug effects / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology
D006514:Hepatitis B Surface Antigens; D020382:Interleukin-18; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; D018664:Interleukin-12; D015237:Dinoprost; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases