Polysaccharide purified from Ganoderma lucidum induced activation and maturation of human monocyte-derived dendritic cells by the NF-κB 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: Society for Leukocyte Biology 01.08.2005
• Subjects: Ganoderma lucidum; IFN‐γ; IL‐10; IL‐12; PS‐G; signal transduction; T cells
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0804481

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)‐β‐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‐γ 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 κB (IκB) kinase and nuclear factor (NF)‐κB activity and also IκBα and p38 mitogen‐activated protein kinase (MAPK) phosphorylation. Further, inhibition of NF‐κB 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.