Research article

BMC Complementary and Alternative Medicine

, 12:119

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Cheng-Li WangAffiliated withDepartment of Biochemical Science and Technology, National Taiwan University
  • , Chiu-Ying LuAffiliated withDepartment of Biochemical Science and Technology, National Taiwan University
  • , Chia-Chen PiAffiliated withDepartment of Biochemical Science and Technology, National Taiwan University
  • , Yu-Jing ZhuangAffiliated withDepartment of Biochemical Science and Technology, National Taiwan University
  • , Ching-Liang ChuAffiliated withGraduate Institute of Immunology, National Taiwan University, College of Medicine
  • , Wen-Hsiung LiuAffiliated withDepartment of Biochemical Science and Technology, National Taiwan University
  • , Chun-Jen ChenAffiliated withDepartment of Biochemical Science and Technology, National Taiwan University Email author 

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