Role for toll-like receptor 4 in TNF-alpha secretion by murine macrophages in response to polysaccharide Krestin, a Trametes versicolor mushroom extract

Woody fungi and yeast preparations show promise in cancer treatment by activating antitumor immune responses. Macrophages (J774A.1) were treated with PSK, Reishi extract, scleroglucan or vehicle control. Pre-incubation with TLR4 blocking antibody inhibited TNF-alpha secretion by both J774A.1 cells and primary splenocytes but had inconclusive effect on scleroglucan-induced secretion of TNF-alpha. PSK induced TNF-alpha and IL-6 secretion by wild type but not by TLR4-deficient peritoneal macrophages. We conclude that constituents from PSK act as ligands for TLR4 receptors leading to induction of TNF-alpha and IL-6 inflammatory cytokines. Receptor-mediated differences may be due to structural differences in beta glucans or non-glucan constituents. (C) 2010 Published by Elsevier B.V.