title: Protein-bound polysaccharide-K induces IL-1β via TLR2 and NLRP3 inflammasome activation.
abstract: 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.
authors: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, WA, USA.
authors: Yi
authors: Y
authors: Yang
authors: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, WA, USA.
authors: Carol
authors: C
authors: Inatsuka
authors: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, WA, USA.
authors: Ekram
authors: E
authors: Gad
authors: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, WA, USA.
authors: Mary L
authors: ML
authors: Disis
authors: Bastyr University, Kenmore, WA, USA.
authors: Leanna J
authors: LJ
authors: Standish
authors: National Center for Natural Products Research, University of Mississippi, University, MS, USA.
authors: Nirmal
authors: N
authors: Pugh
authors: National Center for Natural Products Research, University of Mississippi, University, MS, USA.
authors: David S
authors: DS
authors: Pasco
authors: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, WA, USA hlu@u.washington.edu.
authors: Hailing
authors: H
authors: Lu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D020169:Caspases / Q000096:biosynthesis; D002401:Cathepsin B / Q000502:physiology; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects*; D053583:Interleukin-1beta / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011188:Potassium / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D011509:Proteoglycans; D051195:Toll-Like Receptor 2; C010770:polysaccharide-K; D020169:Caspases; D002401:Cathepsin B; D011188:Potassium
keywords: NLRP3 inflammasome; PSK; TLR2