title: Inflammasomes in the lung.
abstract: Innate immune responses act as first line defences upon exposure to potentially noxious stimuli. The innate immune system has evolved numerous intracellular and extracellular receptors that undertake surveillance for potentially damaging particulates. Inflammasomes are intracellular innate immune multiprotein complexes that form and are activated following interaction with these stimuli. Inflammasome activation leads to the cleavage of pro-IL-1β and release of the pro-inflammatory cytokine, IL-1β, which initiates acute phase pro-inflammatory responses, and other responses are also involved (IL-18, pyroptosis). However, excessive activation of inflammasomes can result in chronic inflammation, which has been implicated in a range of chronic inflammatory diseases. The airways are constantly exposed to a wide variety of stimuli. Inflammasome activation and downstream responses clears these stimuli. However, excessive activation may drive the pathogenesis of chronic respiratory diseases such as severe asthma and chronic obstructive pulmonary disease. Thus, there is currently intense interest in the role of inflammasomes in chronic inflammatory lung diseases and in their potential for therapeutic targeting. Here we review the known associations between inflammasome-mediated responses and the development and exacerbation of chronic lung diseases.
authors.affiliation: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: James W
authors.initials: JW
authors.lastname: Pinkerton
authors.affiliation: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Richard Y
authors.initials: RY
authors.lastname: Kim
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Avril A B
authors.initials: AAB
authors.lastname: Robertson
authors.affiliation: James Hogg Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Hirota
authors.affiliation: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Wood
authors.affiliation: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Darryl A
authors.initials: DA
authors.lastname: Knight
authors.affiliation: Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
authors.affiliation: School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Luke A J
authors.initials: LAJ
authors.lastname: O'Neill
authors.affiliation: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Jay C
authors.initials: JC
authors.lastname: Horvat
authors.affiliation: Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia. Electronic address: Philip.Hansbro@newcastle.edu.au.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
mesh_terms: D020170:Caspase 1 / Q000378:metabolism; D002908:Chronic Disease; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D020382:Interleukin-18 / Q000096:biosynthesis / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology* / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D020170:Caspase 1
keywords: Asthma; Chronic obstructive pulmonary disease; IL-1β; Inflammasome; Lung