title: Hepatitis B virus surface antigen can activate human monocyte-derived dendritic cells by nuclear factor kappa B and p38 mitogen-activated protein kinase mediated signaling.
abstract: Hepatitis B virus Ag (HBsAg), a major antigen of hepatitis B virus (HBV), is also a vaccine component for prevention of HBV infection. Dendritic cells (DCs) of HBV carriers reportedly exhibit functional impairment. In this study, the aim was to investigate the effect of HBsAg on activation of human monocyte-derived dendritic cells (MD-DCs), and the subsequent signal transduction pathway. Treatment of MD-DCs with HBsAg resulted in enhanced cell surface expression of cluster of differentiation 80, CD83, CD86 and major histocompatibility complex class II, and increased interleukin (IL)-12 p40, IL-12p70, and IL-10 production. Furthermore, HBsAg treatment of MD-DCs with HBsAg resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of interferon and IL-10. The pathway of MD-DCs activation by HBsAg was further investigated in the present study. Inhibition of nuclear factor (NF)-kappa B (κB) by helenalin and p38 mitogen-activated protein kinase (MAPK) by SB203580 prevented production of IL-12 p40, IL-12 p70, and IL-10. HBsAg also augmented MAPK phosphorylation. Thus, cytokine secretion of human MD-DCs by HBsAg is blocked by inhibition of the NF-κB and p38 MAPK pathways. Likewise, decreased inhibition of kappa B alpha concentrations and MAPK phosphorylation are critical for MD-DC maturation by HBsAg. These findings may provide a strategy for improving the prophylactic and therapeutic efficacy of vaccines and tumor therapies that utilize these pathways.
authors.affiliation: Institute of Medical Sciences, Tzu-Chi University, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Rong-Hwa
authors.initials: RH
authors.lastname: Jan
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Lin
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Chen
authors.forename: Teng-Yi
authors.initials: TY
authors.lastname: Lin
authors.forename: Ya-Chun
authors.initials: YC
authors.lastname: Hsu
authors.forename: Li-Kuang
authors.initials: LK
authors.lastname: Chen
authors.forename: Bor-Luen
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007372:Interferons / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D006514:Hepatitis B Surface Antigens; D000949:Histocompatibility Antigens Class II; D007378:Interleukins; D016328:NF-kappa B; D007372:Interferons; D048051:p38 Mitogen-Activated Protein Kinases