title: Medicinal mushroom Lingzhi or Reishi, Ganoderma lucidum (W.Curt.:Fr.) P. Karst., beta-glucan induces Toll-like receptors and fails to induce inflammatory cytokines in NF-kappaB inhibitor-treated macrophages.
abstract: Beta-Glucan of medicinal Lingzhi or Reishi mushroom, Ganoderma lucidum (BGG), possesses immunostimulatory and anti-tumor activities. Innate immune cells are activated by the binding of beta-glucan to the dectin-1 receptor. The present study investigated the immunostimulating activities of BGG, including binding to dectin-1, secretion of cytokines and reactive oxygen species, and induction of Toll-like receptors (TLRs) in RAW264.7 mouse macrophages. Reverse transcription-polymerase chain reaction and flow cytometry were used for the cytokine and TLR analyses. A mouse inflammation antibody array was used for protein-level cytokine analysis. BGG bound to dectin-1 and induced RAW264.7 cell secretion of several cytokines, including granulocyte colony-stimulating factor, interleukin (IL)-6, regulated upon activation normal T cell expressed and secreted (RANTES), tissue inhibitor of metalloproteinase-1, and tumor necrosis factor-alpha. The secretion of these cytokines was further increased by the addition of lipopolysaccharide (LPS). BGG also induced both nitric oxide and inducible nitric oxide synthase (iNOS). Treatment with an inhibitor of nuclear factor-kappa B (NF-kappaB) reduced the induction of IL-1, IL-6, and iNOS in a concentration-dependent manner. Expressions of TLR2, TLR4, and TLR6 were increased by BGG treatment, and addition of LPS induced further induction of TLR4 and TLR6. Our result indicates that BGG induces macrophage secretion of inflammatory cytokines, which can be potentiated by the presence of LPS, likely by binding to dectin-1 and TLR-2/6 receptors, which activate NF-kappaB and prompt the secretion of cytokines.
authors.affiliation: Department of Life Sciences, University of Seoul, Seoul 130-743, Korea.
authors.forename: Sainkhuu
authors.initials: S
authors.lastname: Batbayar
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Kim
authors.forename: Ha Won
authors.initials: HW
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020672:I-kappa B Proteins / Q000494:pharmacology*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000302:isolation & purification; D017382:Reactive Oxygen Species / Q000378:metabolism; D020940:Reishi / Q000737:chemistry*; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D015054:Zymosan / Q000378:metabolism / Q000494:pharmacology; D047071:beta-Glucans / Q000276:immunology / Q000378:metabolism*; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D004365:Drugs, Chinese Herbal; D020672:I-kappa B Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D037181:Lectins, C-Type; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D012313:RNA; D017382:Reactive Oxygen Species; D051193:Toll-Like Receptors; D015054:Zymosan; D047071:beta-Glucans; D000099181:Dectin-1; C000606205:Nfkbia protein, mouse