Molecular mechanism of macrophage activation by Exopolysaccharides from liquid culture of Lentinus edodes.
Mushrooms are regarded as one of the well-known foods and biopharmaceutical materials with a great deal of interest. beta-Glucan is the major component of mushrooms that displays various biological activities such as antidiabetic, anticancer, and antihyperlipidemic effects. In this study, we explored the molecular mechanism of its immunostimulatory potency in immune responses of macrophages, using exopolysaccharides prepared from liquid culture of Lentinus edodes. We found that fraction II (F-II), with large molecular weight protein polysaccharides, is able to strongly upregulate the phenotypic functions of macrophages such as phagocytic uptake, ROS/NO production, cytokine expression, and morphological changes. F-II triggered the nuclear translocation of NF-kappaB and activated its upstream signaling cascades such as PI3K/ Akt and MAPK pathways, as assessed by their phosphorylation levels. The function-blocking antibodies to dectin-1 and TLR-2, but not CR3, markedly suppressed F-II-mediated NO production. Therefore, our data suggest that mushroom-derived beta-glucan may exert its immunostimulating potency via activation of multiple signaling pathways.
Lee
Ji Yeon
JY
Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Korea.
Kim
Joo Young
JY
Lee
Yong Gyu
YG
Rhee
Man Hee
MH
Hong
Eock Ki
EK
Cho
Jae Youl
JY
D000818:Animals; D045744:Cell Line, Tumor; D003470:Culture Media / Q000737:chemistry*; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D037181:Lectins, C-Type; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology* / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism; D011134:Polysaccharides / Q000276:immunology*; D020942:Shiitake Mushrooms / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D000099181:Dectin-1
D003470:Culture Media; D016207:Cytokines; D037181:Lectins, C-Type; D008565:Membrane Proteins; D052002:NF-kappa B p50 Subunit; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D011134:Polysaccharides; D051195:Toll-Like Receptor 2; D000099181:Dectin-1; C493486:Tlr2 protein, mouse; C073701:Nfkb1 protein, mouse