A (1→6)-Branched (1→4)-β- d -Glucan from Grifola frondosa Inhibits Lipopolysaccharide-Induced Cytokine Production in RAW264.7 Macrophages by Binding to TLR2 Rather than Dectin-1 or CR3 Receptors
Journal
Journal of Natural Products
Journal Volume
83
Journal Volume
83
Journal Issue
2
Journal Issue
2
Pages
231-242
Start Page
231
End Page
242
ISSN
01633864
Date Issued
2020-02-28
Author(s)
Abstract
Mushroom polysaccharides including β-glucans possess various health-promoting properties and are known to be the major bioactive constituents of Grifola frondosa (GF), which is a popular edible and medicinal mushroom. Dectin-1, a pattern-recognition receptor, is responsible for recognizing β-glucans. In this study, parental RAW264.7 macrophages and Dectin-1-expressing RAW264.7 macrophages were used to investigate the anti-inflammatory activity and receptor involvement of the water-soluble polysaccharides from GF. Results indicated that the high molecular weight fraction of GF (GF70-F1; 1260 kDa) inhibited TNF-α and IL-6 production as well as NF-κB activation in lipopolysaccharide-induced macrophages. Chemical and enzymatic linkage analyses indicated that GF70-F1 mainly contained the known (1→3),(1→6)-β-d-glucan and a polysaccharide not previously isolated from GF, a nondigestible glucan with a β-(1→4)-linked backbone and β-(1→6)-linked branches. The ability of GF70-F1 to inhibit cytokine production was not affected by the expression level of Dectin-1 in cells, and a similar inhibitory activity was observed after removing the (1→3),(1→6)-β-d-glucan from GF70-F1. Blockade of Toll-like receptor 2 (TLR2) but not Dectin-1 or complement receptor 3 (CR3) attenuated the inhibitory activity of GF70-F1. The nondigestible (1→6)-branched (1→4)-β-d-glucan in GF70-F1 may contribute to the anti-inflammatory activity via interacting with TLR2 rather than Dectin-1 or CR3 receptors.
Other Subjects
antiinflammatory agent; arabinose; cell surface receptor; complement component C3 receptor; dectin 1; fucose; galactose; galacturonic acid; gf 70; gf 70f 1; gf 70f 2; glucan; glucose; glucuronic acid; immunoglobulin enhancer binding protein; interleukin 6; laminaran; mannose; pattern recognition receptor; protein synthesis inhibitor; rhamnose; ribose; toll like receptor 2; transcription factor RelA; tumor necrosis factor; unclassified drug; xylose; beta glucan; cytokine; dectin 1; glucan; lectin; lipopolysaccharide; TLR2 protein, human; toll like receptor 2; tumor necrosis factor; animal cell; antiinflammatory activity; Article; cell viability; chemical composition; controlled study; cytokine production; drug protein binding; drug receptor binding; drug structure; Grifola frondosa; linkage analysis; methylation; molecular weight; nonhuman; physical chemistry; protein expression level; protein synthesis inhibition; RAW 264.7 cell line; triple helix; Agaricales; animal; chemical structure; chemistry; drug effect; Grifola; macrophage; metabolism; signal transduction; Agaricales; Animals; beta-Glucans; Cytokines; Glucans; Grifola; Lectins, C-Type; Lipopolysaccharides; Macrophages; Molecular Structure; Signal Transduction; Toll-Like Receptor 2; Tumor Necrosis Factor-alpha
Publisher
American Chemical Society
Type
journal article