Stimulation of TNF- α secretion by Polysaccharide Krestin, a Trametes versicolor mushroom extract, is toll-like receptor 4-dependent and dectin-1 independent

The effects of mycological extracts on inflammatory cytokine secretion in J774A.1 mouse macrophage cell cultures (wild type peritoneal macrophages and TLR4-deficient mice (C57B1/6 TLR4 (-/-)) involving the pathogen-associated molecular pattern recognition (PAMP) receptors TLR-4 and dectin-1 were investigated [1]. Trametes versicolor extract Polysaccharide Krestin (PSK), an extract from Ganoderma lucidum, also known as Reishi, or the secreted polysaccharide scleroglucan from Sclerotium rolfsi all induced TNF-α secretion in J774A.1 cell cultures. TLR-4 blocking antibodies inhibited PSK- and Reishi-induced TNF-α secretion, but not scleroglucan-induced secretion in both J774A.1 cells and primary splenocytes from C57Bl/6 mice. Conversely, dectin-1 blocking antibody inhibited scleroglucan- but not PSK- and Reishi-induced TNF-α secretion. PSK induced TNF-α and IL-6 secretion in wild type but not in TLR4 deficient macrophages (C57B1/6TLR4-/-). Thus, PSK requires TLR-4 receptors for induction of TNF-α and IL-6 inflammatory cytokines, similar to reported Reishi polysaccharide effects [2]. The receptor-mediated differences in signaling for TNF-α secretion between scleroglucan, PSK and Reishi mushroom extracts may be due to conformational differences in β-D-glucans and/or other non-glucan constituents that can activate TLR-4.

References: 1. Werling, D. et al (2003) Vet. Immunol. Immunopathol. 91:1–12

2. Hsu, HY et al. (2004)J. of Immun. 173:5989–5999