The adjuvant effects of high-molecule-weight polysaccharides purified from Antrodia cinnamomea on dendritic cell function and DNA vaccines.
The biological activity of the edible basidiomycete Antrodia cinnamomea (AC) has been studied extensively. Many effects, such as anti-cancer, anti-inflammatory, and antioxidant activities, have been reported from either crude extracts or compounds isolated from AC. However, research addressing the function of AC in enhancing immunity is rare. The aim of the present study is to investigate the active components and the mechanism involved in the immunostimulatory effect of AC. We found that polysaccharides (PS) in the water extract of AC played a major role in dendritic cell (DC) activation, which is a critical leukocyte in initiating immune responses. We further size purified and identified that the high-molecular weight PS fraction (greater than 100 kDa) exhibited the activating effect. The AC high-molecular weight PSs (AC hmwPSs) promoted pro-inflammatory cytokine production by DCs and the maturation of DCs. In addition, DC-induced antigen-specific T cell activation and Th1 differentiation were increased by AC hmwPSs. In studying the molecular mechanism, we confirmed the activation of the MAPK and NF-κB pathways in DCs after AC hmwPSs treatment. Furthermore, we demonstrated that TLR2 and TLR4 are required for the stimulatory activity of AC hmwPSs on DCs. In a mouse tumor model, we demonstrated that AC hmwPSs enhanced the anti-tumor efficacy of the HER-2/neu DNA vaccine by facilitating specific Th1 responses. Thus, we conclude that hmwPSs are the major components of AC that stimulate DCs via the TLR2/TLR4 and NF-κB/MAPK signaling pathways. The AC hmwPSs have potential to be applied as adjuvants.
Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan.
Chi-Chen
CC
Lin
Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
I-Hong
IH
Pan
Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
Yi-Rong
YR
Li
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yi-Gen
YG
Pan
Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
Ming-Kuem
MK
Lin
Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
Yi-Huang
YH
Lu
Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
Hsin-Chieh
HC
Wu
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Ching-Liang
CL
Chu
D000276:Adjuvants, Immunologic; D000818:Animals; D055491:Antrodia / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D062610:Fungal Polysaccharides / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008970:Molecular Weight; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D062610:Fungal Polysaccharides; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D018719:Erb-b2 Receptor Tyrosine Kinases; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D019444:Vaccines, DNA