Immunomodulatory Activity of Polysaccharide from Trametes gibbosa (Pers.) Fr (Basidiomycota, Fungi) Mediated by TLR4 Signaling Pathway

Background: Trametes species possess remarkable immunomodulatory and anticancer effects which are mainly related to the activation of innate immune receptors by their polysaccharide constituents. In this study, we investigate the effect of Trametes gibbosa (Pers.) Fr. polysaccharide fraction (TGP) on activation of TLR-4 receptor and subsequent release of IL-8 in HEK-Blue (TM) hTLR4 cells. Materials and Methods: The polysaccharide fraction was purified using ethanol precipitation and dialysis methods. The total sugar content and monosaccharide composition were analyzed by phenol-sulfuric acid and chromatographic methods. FT-IR spectroscopy was also performed for structure characterization of the polysaccharide. The activation of TLR4 was determined by measuring the secreted embryonic alkaline phosphatase in the culture media. Results: The results indicated that the total sugar content of TGP was about 90%, which glucose was the major constituents. FT-IR analysis showed the characteristic bands of polysaccharides. TGP was able to activate the TLR-4 signaling pathway in a dose-dependent manner. Moreover, the significant increase of IL-8 was observed in cells treating with TGP. The HEK-Blue Null2 (TM) reporter cells lacking TLR4, did not respond to LPS and TGP. Conclusion: The results suggest that TLR4 signaling cascade serve as targets for immunomodulatory activity of T. gibbosa which could address the anticancer properties of Trametes species.