title: Mechanism of macrophage activation induced by polysaccharide from Cordyceps militaris culture broth.
abstract: Mushroom-derived polysaccharides have been shown to stimulate immune responses. Our previous report showed that the novel polysaccharide PLCM isolated from the culture broth of Cordyceps militaris could induce nitric oxide production in the murine macrophage-like cell line RAW264.7. In this study, we show that PLCM enhances immunostimulatory activities such as the release of toxic molecules (nitric oxide and reactive oxygen species), secretion of the cytokine tumor necrosis factor (TNF)-α, and phagocytic uptake in RAW264.7 macrophages. In addition, all the specific inhibitors against the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) (SN50, BAY11-7082, PD98059, SP600125 and SB203580) markedly suppressed the nitric oxide production and phagocytic uptake induced by PLCM. Moreover, antibodies specific to the extracellular domain of Toll-like receptor-2, Toll-like receptor-4 or the macrophage receptor Dectin-1 significantly attenuated PLCM-induced secretion of TNF-α. Our results indicate that the C. militaris polysaccharide activates macrophages through the MAPKs and NF-κB signaling pathways via Toll-like receptor 2, Toll-like receptor 4, and Dectin-1.
authors: Department of Bioengineering and Technology, Kangwon National University, 192-1, Hyoja-2-dong, Chuncheon 200-701, Gangwon-do, Republic of Korea; National Institute of Biological Resources, Incheon 404-708, Republic of Korea.
authors: Jong Seok
authors: JS
authors: Lee
authors: Department of Bioengineering and Technology, Kangwon National University, 192-1, Hyoja-2-dong, Chuncheon 200-701, Gangwon-do, Republic of Korea.
authors: Duck Soo
authors: DS
authors: Kwon
authors: Department of Bioengineering and Technology, Kangwon National University, 192-1, Hyoja-2-dong, Chuncheon 200-701, Gangwon-do, Republic of Korea.
authors: Ki Rim
authors: KR
authors: Lee
authors: Department of Bioengineering and Technology, Kangwon National University, 192-1, Hyoja-2-dong, Chuncheon 200-701, Gangwon-do, Republic of Korea.
authors: Jun Myoung
authors: JM
authors: Park
authors: Department of Bioengineering and Technology, Kangwon National University, 192-1, Hyoja-2-dong, Chuncheon 200-701, Gangwon-do, Republic of Korea.
authors: Suk-Jin
authors: SJ
authors: Ha
authors: Department of Bioengineering and Technology, Kangwon National University, 192-1, Hyoja-2-dong, Chuncheon 200-701, Gangwon-do, Republic of Korea. Electronic address: ekhong@kangwon.ac.kr.
authors: Eock Kee
authors: EK
authors: Hong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D032661:Cordyceps / Q000737:chemistry*; D003470:Culture Media / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D003470:Culture Media; D016328:NF-kappa B; D011134:Polysaccharides; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases
keywords: MAPKs; Macrophage; NF-κB; PRRs; Polysaccharide