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

Fitoterapia. 2010 Oct;81(7):914-9. doi: 10.1016/j.fitote.2010.06.002. Epub 2010 Jun 13.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Biological Products / pharmacology*
  • Glucans
  • Interleukin-6 / metabolism
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proteoglycans / chemistry
  • Proteoglycans / pharmacology*
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / metabolism
  • Toll-Like Receptor 4 / metabolism*
  • Trametes / chemistry*
  • Tumor Necrosis Factor-alpha / metabolism*


  • Adjuvants, Immunologic
  • Biological Products
  • Glucans
  • Interleukin-6
  • Proteoglycans
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • scleroglucan
  • polysaccharide-K