title: Pleurotus citrinopileatus polysaccharide induces activation of human dendritic cells through multiple pathways.
abstract: Many edible mushrooms have become attractive as "health foods" and as source materials for immunomodulators. To increase our insight in the immune-modulatory properties of a polysaccharide of the oyster mushroom Pleurotus citrinopileatus, PCPS, we analyzed its effects on the function of human dendritic cells (DCs). We showed that PCPS induces upregulation of the surface maturation markers CD80, CD86 and HLA-DR on DCs, indicating its potential to induce DC maturation. In addition, PCPS stimulates DCs to secrete the pro-inflammatory cytokines TNF, IL-1β, IL-6 and IL-12, as well as the anti-inflammatory cytokine IL-10, and induces enhanced mRNA levels of the chemokines CCL2, CCL3, CCL8, CXCL9, CXCL10, and LTA. The secretion of TNF and IL-12 by PCPS-activated DCs could significantly be decreased by an anti-Dectin-1 antibody, as well as by a Syk kinase and a Raf-1 inhibitor, indicating that PCPS induces Dectin-1 signaling at least partly through the Syk- and the Raf-1-dependent pathways in DCs. Structural analysis of PCPS suggests that this polysaccharide is a β-1,3-branched β-1,6-glucan, which is in line with its capacity to activate Dectin-1. We showed that PCPS can induce TLR2 and TLR4, but not TLR3, signaling using TLR-HEK293 reporter cell lines. In human DCs, the effect of PCPS was additively increased by TLR4 activation, and synergistically enhanced by stimulation of TLR2, suggesting that interaction of PCPS with these TLRs contributes to the observed DC modulation. In conclusion, PCPS has the capacity to activate human DCs via multiple pathways.
authors: Department of Applied Biological Chemistry, The Graduate School of Agriculture, Meijo University, Nagoya 468-8502, Japan; Department of Molecular Cell Biology and Immunology, VU University Medical Center O2 Building, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands. Electronic address: minato@meijo-u.ac.jp.
authors: Ken-Ichiro
authors: KI
authors: Minato
authors: Department of Molecular Cell Biology and Immunology, VU University Medical Center O2 Building, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.
authors: Lisa C
authors: LC
authors: Laan
authors: Department of Applied Biological Chemistry, The Graduate School of Agriculture, Meijo University, Nagoya 468-8502, Japan.
authors: Akihiro
authors: A
authors: Ohara
authors: Department of Molecular Cell Biology and Immunology, VU University Medical Center O2 Building, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.
authors: Irma
authors: I
authors: van Die
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D062610:Fungal Polysaccharides / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000378:metabolism; D020076:Pleurotus; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D062610:Fungal Polysaccharides; D007155:Immunologic Factors; D037181:Lectins, C-Type; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C546929:CLEC7A protein, human; D000099181:Dectin-1; C495342:TLR2 protein, human; C495345:TLR4 protein, human
keywords: Dectin-1; Human dendritic cells; Pleurotus citrinopileatus; TLR2; TLR4; β-Glucan