title: Polysaccharide purified from Ganoderma lucidum induced activation and maturation of human monocyte-derived dendritic cells by the NF-kappaB and p38 mitogen-activated protein kinase pathways.
abstract: Ganoderma lucidum, a fungus native to China, has been widely used to promote health and longevity in the Chinese. The polysaccharide component with a branched (1-->6)-beta-D-glucan moiety of G. lucidum (PS-G) has been reported to exert anti-tumor activity and activation of natural killer cells. In this study, we investigated the effects of PS-G on human monocyte-derived dendritic cells (DC). Treatment of DC with PS-G resulted in the enhanced cell-surface expression of CD80, CD86, CD83, CD40, CD54, and human leukocyte antigen (HLA)-DR, as well as the enhanced production of interleukin (IL)-12p70, p40, and IL-10 and also IL-12p35, p40, and IL-10 mRNA expression, and the capacity for endocytosis was suppressed in DC. In addition, treatment of DC with PS-G resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of interferon-gamma and IL-10. Neutralization with antibodies against Toll-like receptor (TLR)-4 inhibited the PS-G-induced production of IL-12 p40 and IL-10, suggesting a vital role for TLR-4 in signaling DC upon incubation with PS-G. Further study showed that PS-G was able to augment inhibitor of kappaB (IkappaB) kinase and nuclear factor (NF)-kappaB activity and also IkappaB alpha and p38 mitogen-activated protein kinase (MAPK) phosphorylation. Further, inhibition of NF-kappaB by helenalin and p38 MAPK by SB98059 prevented the effects of PS-G in the expression of CD80, CD86, CD83, CD40, CD54, and HLA-DR and production of IL-12p70, p40, and IL-10 in various degrees. Taken together, our data demonstrate that PS-G can effectively promote the activation and maturation of immature DC, suggesting that PS-G may possess a potential in regulating immune responses.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Lin
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Liang
authors.forename: Shiuh-Sheng
authors.initials: SS
authors.lastname: Lee
authors.forename: Bor-Luen
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D020940:Reishi / Q000737:chemistry*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006684:HLA-DR Antigens; D020672:I-kappa B Proteins; D007378:Interleukins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011134:Polysaccharides; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000072000:NF-KappaB Inhibitor alpha; D048051:p38 Mitogen-Activated Protein Kinases