title: The NLRP3 inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases.
abstract: The concept of the inflammasome, a macromolecular complex sensing cell stress or danger signals and initiating inflammation, was first introduced approximately a decade ago. Priming and activation of these intracellular protein platforms trigger the maturation of pro-inflammatory chemokines and cytokines, most notably, interleukin-1β (IL-1β) and IL-18, to promulgate innate immune defenses. Although classically studied in models of gout, Type II diabetes, Alzheimer's disease, and multiple sclerosis, the importance and mechanisms of action of inflammasome priming and activation have recently been elucidated in cells of the respiratory tract where they modulate the responses to a number of inhaled pathogenic particles and fibres. Most notably, inflammasome activation appears to regulate the balance between tissue repair and inflammation after inhalation of pathogenic pollutants such as asbestos, crystalline silica (CS), and airborne particulate matter (PM). Different types of fibres and particles may have distinct mechanisms of inflammasome interaction and outcome. This review summarizes the structure and function of inflammasomes, the interplay between various chemokines and cytokines and cell types of the lung and pleura after inflammasome activation, and the events leading to the development of non-malignant (allergic airway disease and chronic obstructive pulmonary disease (COPD), asbestosis, silicosis) and malignant (mesothelioma, lung cancer) diseases by pathogenic particulates. In addition, it emphasizes the importance of communication between cells of the immune system, target cells of these diseases, and components of the extracellular matrix (ECM) in regulation of inflammasome-mediated events.
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, 111 Colchester Avenue, Burlington, 05401, VT, USA.
authors.forename: Mutlay
authors.initials: M
authors.lastname: Sayan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, 05405, VT, USA. brooke.mossman@uvm.edu.
authors.forename: Brooke T
authors.initials: BT
authors.lastname: Mossman
mesh_terms: D000818:Animals; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D008171:Lung Diseases / Q000139:chemically induced*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D052638:Particulate Matter / Q000633:toxicity; D011014:Pneumonia / Q000139:chemically induced*; D012822:Silicon Dioxide / Q000633:toxicity
chemical_list: D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D052638:Particulate Matter; D012822:Silicon Dioxide
keywords: Airborne particulate matter; Allergic airway disease; Asbestos; Fibrosis; Inflammation; Lung cancer; Mesothelioma; Nanotubes; Silica