The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia

Jie Liao, Vishal S. Kapadia, L. Steven Brown, Naeun Cheong, Christopher Longoria, Dan Mija, Mrithyunjay Ramgopal, Julie Mirpuri, Donald C Mccurnin, Rashmin C. Savani

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish (US)
Article number8977
JournalNature Communications
Volume6
DOIs
StatePublished - Nov 27 2015

Fingerprint

Inflammasomes
Bronchopulmonary Dysplasia
hyperoxia
Chemical activation
activation
mice
Caspase 1
Hyperoxia
Inflammation
baboons
Premature Infants
pathogenesis
Pulmonary diseases
Interleukin-1 Receptors
Glyburide
lungs
Papio
Respiratory Insufficiency
Lung Diseases
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Liao, J., Kapadia, V. S., Brown, L. S., Cheong, N., Longoria, C., Mija, D., ... Savani, R. C. (2015). The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia. Nature Communications, 6, [8977]. https://doi.org/10.1038/ncomms9977

The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia. / Liao, Jie; Kapadia, Vishal S.; Brown, L. Steven; Cheong, Naeun; Longoria, Christopher; Mija, Dan; Ramgopal, Mrithyunjay; Mirpuri, Julie; Mccurnin, Donald C; Savani, Rashmin C.

In: Nature Communications, Vol. 6, 8977, 27.11.2015.

Research output: Contribution to journalArticle

Liao, J, Kapadia, VS, Brown, LS, Cheong, N, Longoria, C, Mija, D, Ramgopal, M, Mirpuri, J, Mccurnin, DC & Savani, RC 2015, 'The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia', Nature Communications, vol. 6, 8977. https://doi.org/10.1038/ncomms9977
Liao, Jie ; Kapadia, Vishal S. ; Brown, L. Steven ; Cheong, Naeun ; Longoria, Christopher ; Mija, Dan ; Ramgopal, Mrithyunjay ; Mirpuri, Julie ; Mccurnin, Donald C ; Savani, Rashmin C. / The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia. In: Nature Communications. 2015 ; Vol. 6.
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