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

• Published in: Journal of leukocyte biology Vol. 78; no. 2; pp. 533 - 543
• Main Authors: Lin, Yu-Li, Liang, Yu-Chih, Lee, Shiuh-Sheng, Chiang, Bor-Luen
• Format: Journal Article
• Language: English
• Published: United States 01.08.2005
• Subjects: Antibodies, Monoclonal - pharmacology; Antigens, CD - biosynthesis; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cells, Cultured; Dendritic Cells - cytology; Dendritic Cells - physiology; HLA-DR Antigens - biosynthesis; Humans; I-kappa B Proteins - metabolism; Interleukins - biosynthesis; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Membrane Glycoproteins - antagonists & inhibitors; Monocytes - cytology; Monocytes - physiology; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Polysaccharides - chemistry; Polysaccharides - isolation & purification; Polysaccharides - pharmacology; Receptors, Cell Surface - antagonists & inhibitors; Reishi - chemistry; Toll-Like Receptor 4; Toll-Like Receptors
• ISSN: 0741-5400; 1938-3673

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.