title: Nickel induces interleukin-1β secretion via the NLRP3-ASC-caspase-1 pathway.
abstract: Exposure to nickel (Ni(2+)) can trigger allergic reactions in susceptible individuals, which is widely accepted as the major cause of allergic contact hypersensitivity (CHS) worldwide. Although Ni(2+)-induced proinflammatory responses clearly play a pivotal role in CHS, the underlying molecular mechanism has not been fully defined. Here we report that Ni(2+) activates the NLRP3-ASC-caspase-1 immune signaling pathway in antigen-presenting cells, leading to the proteolytic processing and secretion of a proinflammatory cytokine, interleukin-1β (IL-1β). The activation of this signaling axis is independent of phagolysosome-cathepsin B pathway. Instead, Ni(2+) induces mitochondrial reactive oxygen species accumulation and cation fluxes, both of which are required for activating the NLRP3-ASC-caspase-1 pathway. Together, these results identified a novel innate immune signaling pathway (NLRP3-ASC-caspase-1-IL-1β) activated by Ni(2+) and provided a mechanistic basis for optimizing the therapeutic intervention against Ni(2+)-induced allergy in patients.
authors.affiliation: Department of Biotechnology, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao, Hebei, 066004, China.
authors.forename: Xiujin
authors.initials: X
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Zhong
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000201:enzymology / Q000209:etiology* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D058847:Inflammasomes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009532:Nickel / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C508585:IL1B protein, human; C587672:IL1B protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C492716:Nlrp3 protein, mouse; C402202:PYCARD protein, human; C498534:Pycard protein, mouse; D017382:Reactive Oxygen Species; C022838:nickel chloride; D009532:Nickel; D020170:Caspase 1