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Open Access Research article

Extracellular polysaccharides produced by Ganoderma formosanum stimulate macrophage activation via multiple pattern-recognition receptors

Cheng-Li Wang1, Chiu-Ying Lu1, Chia-Chen Pi1, Yu-Jing Zhuang1, Ching-Liang Chu2, Wen-Hsiung Liu1 and Chun-Jen Chen1*

Author affiliations

1 Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan, 10617, Republic of China

2 Graduate Institute of Immunology, National Taiwan University, College of Medicine, Taipei, Taiwan, 100, Republic of China

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Citation and License

BMC Complementary and Alternative Medicine 2012, 12:119  doi:10.1186/1472-6882-12-119

Published: 10 August 2012

Abstract

Background

The fungus of Ganoderma is a traditional medicine in Asia with a variety of pharmacological functions including anti-cancer activities. We have purified an extracellular heteropolysaccharide fraction, PS-F2, from the submerged mycelia culture of G. formosanum and shown that PS-F2 exhibits immunostimulatory activities. In this study, we investigated the molecular mechanisms of immunostimulation by PS-F2.

Results

PS-F2-stimulated TNF-α production in macrophages was significantly reduced in the presence of blocking antibodies for Dectin-1 and complement receptor 3 (CR3), laminarin, or piceatannol (a spleen tyrosine kinase inhibitor), suggesting that PS-F2 recognition by macrophages is mediated by Dectin-1 and CR3 receptors. In addition, the stimulatory effect of PS-F2 was attenuated in the bone marrow-derived macrophages from C3H/HeJ mice which lack functional Toll-like receptor 4 (TLR4). PS-F2 stimulation triggered the phosphorylation of mitogen-activated protein kinases JNK, p38, and ERK, as well as the nuclear translocation of NF-κB, which all played essential roles in activating TNF-α expression.

Conclusions

Our results indicate that the extracellular polysaccharides produced by G. formosanum stimulate macrophages via the engagement of multiple pattern-recognition receptors including Dectin-1, CR3 and TLR4, resulting in the activation of Syk, JNK, p38, ERK, and NK-κB and the production of TNF-α.

Keywords:
Ganoderma formosanum; Polysaccharide; Immunostimulatory; Macrophage; Pattern-recognition receptor