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 | Christian D Ellson, Rebecca Dunmore, Cory M Hogaboam, Matthew A Sleeman, Lynne A Murray |
Journal | American journal of respiratory cell and molecular biology
(Am J Respir Cell Mol Biol)
Vol. 51
Issue 2
Pg. 163-8
(Aug 2014)
ISSN: 1535-4989 [Electronic] United States |
PMID | 24749648
(Publication Type: Journal Article, Review)
|
Chemical References |
- Inflammation Mediators
- Receptors, Immunologic
|
Topics |
- Animals
- Apoptosis
- Host-Pathogen Interactions
- Humans
- Idiopathic Pulmonary Fibrosis
(genetics, immunology, metabolism, microbiology, pathology)
- Inflammation Mediators
(metabolism)
- Lung
(immunology, metabolism, microbiology, pathology)
- Necrosis
- Prognosis
- Receptors, Immunologic
(metabolism)
- Risk Factors
- Signal Transduction
|