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 and Rashmin C. Savani ()
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Jie Liao: Center for Pulmonary & Vascular Biology, University of Texas Southwestern Medical Center
Vishal S. Kapadia: University of Texas Southwestern Medical Center
L. Steven Brown: Health Systems Research, Parkland Health and Hospital System
Naeun Cheong: Center for Pulmonary & Vascular Biology, University of Texas Southwestern Medical Center
Christopher Longoria: Center for Pulmonary & Vascular Biology, University of Texas Southwestern Medical Center
Dan Mija: Center for Pulmonary & Vascular Biology, University of Texas Southwestern Medical Center
Mrithyunjay Ramgopal: Center for Pulmonary & Vascular Biology, University of Texas Southwestern Medical Center
Julie Mirpuri: Center for Pulmonary & Vascular Biology, University of Texas Southwestern Medical Center
Donald C. McCurnin: University of Texas Health Sciences Center at San Antonio and The Southwest Foundation for Biomedical Research
Rashmin C. Savani: Center for Pulmonary & Vascular Biology, University of Texas Southwestern Medical Center

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9977

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