title: Activation of NLRP3 inflammasome by crystalline structures via cell surface contact.
abstract: Crystalline structures activate the NLRP3 inflammasome, leading to the production of IL-1β, however, the molecular interactions responsible for NLRP3 activation are not fully understood. Cathepsin B release from the ruptured phagolysosome and potassium ion efflux have been suggested to be critical for this activation. Here, we report that Cathepsin B redistribution was not a crucial event in crystal-induced IL-1β production. Silica and monosodium urate crystal-treated macrophages with undisturbed lysosomes demonstrated strong co-localization of ASC and Caspase-1, indicative of NLRP3 inflammasome activation. Importantly, we provided evidence to suggest that macrophage cell membrane binding to immobilized crystals was sufficient to induce IL-1β release, and this activation of the NLRP3 inflammasome was inhibited by blocking potassium efflux. Therefore, this work reveals additional complexity in crystalline structure-mediated NLRP3 inflammasome regulations.
authors.affiliation: Department of Microbiology, Immunology &Infectious Diseases and Snyder Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Aswin
authors.initials: A
authors.lastname: Hari
authors.affiliation: Department of Basic Medical Sciences, School of Medicine; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Immunology &Infectious Diseases and Snyder Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Department of Microbiology, Immunology &Infectious Diseases and Snyder Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Pascal
authors.initials: P
authors.lastname: Detampel
authors.affiliation: Department of Microbiology, Immunology &Infectious Diseases and Snyder Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Stenner
authors.affiliation: Department of Microbiology, Immunology &Infectious Diseases and Snyder Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Anutosh
authors.initials: A
authors.lastname: Ganguly
authors.affiliation: 1] Department of Microbiology, Immunology &Infectious Diseases and Snyder Institute, University of Calgary, Calgary, Alberta, Canada [2] Department of Basic Medical Sciences, School of Medicine; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D002401:Cathepsin B; D020170:Caspase 1