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Published online before print May 13, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0804481

Received for publication August 31, 2004.
Revised April 7, 2005.
Accepted for publication April 13, 2005.

Article

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

Yu-Li Lin ^*, Yu-Chih Liang , Shiuh-Sheng Lee , and Bor-Luen Chiang ^*@

*Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Republic of China; Graduate Institute of Biomedical Technology, College of Medicine, Taipei Medical University, Taiwan, Republic of China; and Department of Biochemistry, National Yang-Ming University, Taipei, Taiwan, Republic of China

^@ To whom correspondence should be addressed. E-mail: gicmbor{at}ha.mc.ntu.edu.tw.

	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 (16)--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.

Key Words: PS-G • signal transduction • T cells • IL-10 • IL-12 • IFN-

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