title: Extracellular polysaccharides produced by Ganoderma formosanum stimulate macrophage activation via multiple pattern-recognition receptors.
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.
authors.affiliation: Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan, 10617, Republic of China.
authors.forename: Cheng-Li
authors.initials: CL
authors.lastname: Wang
authors.forename: Chiu-Ying
authors.initials: CY
authors.lastname: Lu
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Pi
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Zhuang
authors.forename: Ching-Liang
authors.initials: CL
authors.lastname: Chu
authors.forename: Wen-Hsiung
authors.initials: WH
authors.lastname: Liu
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D005260:Female; D032902:Ganoderma / Q000737:chemistry / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011134:Polysaccharides / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D011134:Polysaccharides; D051192:Receptors, Pattern Recognition