title: Danger-associated molecular patterns and danger signals in idiopathic pulmonary fibrosis.
abstract: The chronic debilitating lung disease, idiopathic pulmonary fibrosis (IPF), is characterized by a progressive decline in lung function, with a median mortality rate of 2-3 years after diagnosis. IPF is a disease of unknown cause and progression, and multiple pathways have been demonstrated to be activated in the lungs of these patients. A recent genome-wide association study of more than 1,000 patients with IPF identified genes linked to host defense, cell-cell adhesion, and DNA repair being altered due to fibrosis (Fingerlin, et al. Nat Genet 2013;45:613-620). Further emerging data suggest that the respiratory system may not be a truly sterile environment, and it exhibits an altered microbiome during fibrotic disease (Molyneaux and Maher. Eur Respir Rev 2013;22:376-381). These altered host defense mechanisms might explain the increased susceptibility of patients with IPF to microbial- and viral-induced exacerbations. Moreover, chronic epithelial injury and apoptosis are key features in IPF, which might be mediated, in part, by both pathogen-associated (PA) and danger-associated molecular patterns (MPs). Emerging data indicate that both PAMPs and danger-associated MPs contribute to apoptosis, but not necessarily in a manner that allows for the removal of dying cells, without further exacerbating inflammation. In contrast, both types of MPs drive cellular necrosis, leading to an exacerbation of lung injury and/or infection as the debris promotes a proinflammatory response. Thus, this Review focuses on the impact of MPs resulting from infection-driven apoptosis and necrosis during chronic fibrotic lung disease.
authors.affiliation: 1 MedImmune Ltd, Granta Park, Cambridge, United Kingdom; and.
authors.forename: Christian D
authors.initials: CD
authors.lastname: Ellson
authors.forename: Rebecca
authors.initials: R
authors.lastname: Dunmore
authors.forename: Cory M
authors.initials: CM
authors.lastname: Hogaboam
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Sleeman
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Murray
mesh_terms: D000818:Animals; D017209:Apoptosis; D054884:Host-Pathogen Interactions; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D009336:Necrosis; D011379:Prognosis; D011971:Receptors, Immunologic / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D018836:Inflammation Mediators; D011971:Receptors, Immunologic
keywords: bleomycin; epithelium; immune response; sterile inflammation