title: The role of the inflammasome in fibrotic respiratory diseases.
abstract: Fibrotic respiratory diseases severely disrupt lung function and currently have an extremely poor prognosis. This is attributable to the limited amount of treatment options available, in part due to our lack of understanding of the mechanisms driving disease pathogenesis. Although the majority of cases appear to be idiopathic, a number of factors are known to cause pulmonary fibrosis, such as the inhalation of silica crystals (silicosis), asbestos fibers (asbestosis) and certain drugs such as bleomycin. Evidence suggests that the inhalation of such substances can induce the formation of the NLRP3 inflammasome; a multimeric protein complex responsible for the activation of caspase-1 and maturation of the proinflammatory cytokines IL-1b and IL-18. Moreover, data suggests that inhibition of the inflammasome activation pathway and/or inflammasome-mediated cytokines can attenuate the fibrotic response in in vitro and in vivo models of disease. In this review, we discuss the evidence suggesting that the NLRP3 inflammasome plays an important role in the pathogenesis of fibrotic respiratory diseases, and the potential mechanisms by which activation of the NLRP3 inflammasome may occur. It is possible that fibrotic respiratory diseases with a known cause may share a common mechanism with idiopathic pulmonary fibrosis, providing possible strategies for future drug therapies.
authors.affiliation: Immunology Research, New Medicines UCB Pharma, Slough, UK - m.birrell@imperial.ac.uk.
authors.forename: J
authors.initials: J
authors.lastname: Rastrick
authors.forename: M
authors.initials: M
authors.lastname: Birrell
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D001195:Asbestosis / Q000209:etiology*; D001761:Bleomycin / Q000009:adverse effects; D002352:Carrier Proteins / Q000502:physiology*; D020170:Caspase 1 / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000502:physiology*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011658:Pulmonary Fibrosis / Q000209:etiology*; D012829:Silicosis / Q000209:etiology*
chemical_list: D000903:Antibiotics, Antineoplastic; D002352:Carrier Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D001761:Bleomycin; D020170:Caspase 1