Protein-bound polysaccharide-K induces IL-1β via TLR2 and NLRP3 inflammasome activation

• Published in: Innate immunity (London, England) England), 2014-11, Vol.20 (8), p.857-866
• Main Authors: Yang, Yi, Inatsuka, Carol, Gad, Ekram, Disis, Mary L, Standish, Leanna J, Pugh, Nirmal, Pasco, David S, Lu, Hailing
• Format: Article
• Language: English
• Subjects: Animals; Carrier Proteins - biosynthesis; Carrier Proteins - drug effects; Carrier Proteins - genetics; Caspases - biosynthesis; Cathepsin B - physiology; Humans; Inflammasomes - drug effects; Interleukin-1beta - biosynthesis; Leukocytes, Mononuclear - drug effects; Lysosomes - drug effects; Lysosomes - metabolism; Macrophages - drug effects; Mice; Mice, Inbred C57BL; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Potassium - metabolism; Proteoglycans - pharmacology; Toll-Like Receptor 2 - biosynthesis; Toll-Like Receptor 2 - drug effects; Toll-Like Receptor 2 - genetics; Trametes versicolor
• ISSN: 1753-4259; 1753-4267
• DOI: 10.1177/1753425913513814

Inflammasome activation has been shown to regulate both innate and adaptive immune responses. It is important to investigate whether immune-enhancing natural products can also activate inflammasome. The current study examined the potential of protein-bound polysaccharide-K (PSK), a hot water extract from Trametes versicolor, to activate inflammasome. Using THP-1 cells, we have demonstrated that PSK induces both pro-IL-1β and mature IL-1β in THP-1 cells in a caspase 1- and NLRP3-dependent manner. PSK also induces IL-1β and IL-18 in human PBMC. Cathepsin B is required for PSK-induced inflammasome activation as CA-074-Me, a cathepsin B inhibitor, significantly decreased PSK-induced IL-1β. PSK induces NLRP3 at both mRNA and protein level. Comparison of PSK-induced IL-1β in bone marrow-derived macrophages from wild type C57BL/6 mice, TLR2-/-, P2X7R-/- and NLRP3-/- mice demonstrated that PSK-induced IL-1β is dependent on both TLR2 and NLRP3. P2X7R is not required for PSK-induced inflammasome activation, but enhances PSK-induced caspase-1 activation and IL-1β induction. Altogether, these results demonstrated that PSK induces inflammasome activation and production of IL-1β in a TLR2- and NLRP3-dependent mechanism. These results provide novel insights into the mechanisms of the immune modulatory effects of PSK.