BACKGROUND/AIMS: 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.
BACKGROUND/AIMS: 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.
Authors: John E Tavis; Xiaohong Cheng; Yuan Hu; Michael Totten; Feng Cao; Eleftherios Michailidis; Rajeev Aurora; Marvin J Meyers; E Jon Jacobsen; Michael A Parniak; Stefan G Sarafianos Journal: PLoS Pathog Date: 2013-01-22 Impact factor: 6.823