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The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia
- Source :
- Nature communications. 6
- Publication Year :
- 2015
-
Abstract
- The pathogenesis of bronchopulmonary dysplasia (BPD), a devastating lung disease in preterm infants, includes inflammation, the mechanisms of which are not fully characterized. Here we report that the activation of the NLRP3 inflammasome is associated with the development of BPD. Hyperoxia-exposed neonatal mice have increased caspase-1 activation, IL1β and inflammation, and decreased alveolarization. Nlrp3(-/-) mice have no caspase-1 activity, no IL1β, no inflammatory response and undergo normal alveolarization. Treatment of hyperoxia-exposed mice with either IL1 receptor antagonist to block IL1β or glyburide to block the Nlrp3 inflammasome results in decreased inflammation and increased alveolarization. Ventilated preterm baboons show activation of the NLRP3 inflammasome with increased IL1β:IL1ra ratio. The IL1β:IL1ra ratio in tracheal aspirates from preterm infants with respiratory failure is predictive of the development of BPD. We conclude that early activation of the NLRP3 inflammasome is a key mechanism in the development of BPD, and represents a novel therapeutic target for BPD.
- Subjects :
- Inflammasomes
Interleukin-1beta
General Physics and Astronomy
Pathogenesis
Cohort Studies
Mice
Glyburide
Prospective Studies
Lung
Bronchopulmonary Dysplasia
Mice, Knockout
Multidisciplinary
integumentary system
Caspase 1
Inflammasome
respiratory system
medicine.anatomical_structure
medicine.symptom
Bronchoalveolar Lavage Fluid
Infant, Premature
medicine.drug
Blotting, Western
Inflammation
Hyperoxia
Real-Time Polymerase Chain Reaction
General Biochemistry, Genetics and Molecular Biology
Article
mental disorders
Acetylglucosaminidase
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Animals
Humans
Peroxidase
business.industry
Infant, Newborn
General Chemistry
medicine.disease
Interleukin 1 Receptor Antagonist Protein
Interleukin 1 receptor antagonist
Respiratory failure
Bronchopulmonary dysplasia
Animals, Newborn
Immunology
Immunoglobulin A, Secretory
business
Carrier Proteins
Papio
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....f4600959eef50c1f177f3de0904d5df2