title: Role for toll-like receptor 4 in TNF-alpha secretion by murine macrophages in response to polysaccharide Krestin, a Trametes versicolor mushroom extract.
abstract: Woody fungi and yeast preparations show promise in cancer treatment by activating anti-tumor 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.
authors.affiliation: Bastyr University, Department of Basic Sciences, School of Natural Health Sciences, Kenmore, WA 98028, USA. lprice@bastyr.edu
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Price
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Wenner
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Sloper
authors.forename: Joel W
authors.initials: JW
authors.lastname: Slaton
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Novack
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001688:Biological Products / Q000494:pharmacology*; D005936:Glucans; D015850:Interleukin-6 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011509:Proteoglycans / Q000737:chemistry / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D055454:Trametes / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D001688:Biological Products; D005936:Glucans; D015850:Interleukin-6; D011509:Proteoglycans; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C045938:scleroglucan; C010770:polysaccharide-K