Polysaccharide Purified from Ganoderma Lucidum Induced Activation and Maturation of Human Monocyte-Derived Dendritic Cells by the Nf-B and P38 Mitogen-Activated Protein Kinase Pathways

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 (16)-ß-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- 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 B (IB) kinase and nuclear factor (NF)-B activity and also IB and p38 mitogen-activated protein kinase (MAPK) phosphorylation. Further, inhibition of NF-B 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