Cyclooxygenase-2 in newborn hyperoxic lung injury

Rodney D. Britt, Markus Velten, Trent E. Tipple, Leif D. Nelin, Lynette K. Rogers

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Supraphysiological O2 concentrations, mechanical ventilation, and inflammation significantly contribute to the development of bronchopulmonary dysplasia (BPD).Exposure of newborn mice to hyperoxia causes inflammation and impaired alveolarization similar to that seen in infants with BPD.Previously, we demonstrated that pulmonary cyclooxygenase-2 (COX-2) protein expression is increased in hyperoxia-exposed newborn mice.The present studies were designed to define the role of COX-2 in newborn hyperoxic lung injury.We tested the hypothesis that attenuation of COX-2 activity would reduce hyperoxia-induced inflammation and improve alveolarization.Newborn C3H/HeN micewere injected daily with vehicle, aspirin (nonselective COX-2 inhibitor), or celecoxib (selective COX-2 inhibitor) for the first 7 days of life.Additional studies utilized wild-type (C57Bl/6, COX-2+/+), heterozygous (COX-2+/-), and homozygous (COX-2-/-) transgenic mice.Micewere exposed to room air (21% O2) or hyperoxia (85% O2) for 14 days.Aspirin-injected and COX-2-/- pups had reduced levels of monocyte chemoattractant protein (MCP-1) in bronchoalveolar lavage fluid (BAL).Both aspirin and celecoxib treatment reduced macrophage numbers in the alveolar walls and air spaces.Aspirin and celecoxib treatment attenuated hyperoxia-induced COX activity, including altered levels of prostaglandin (PG)D2 metabolites.Decreased COX activity, however, did not prevent hyperoxia-induced lung developmental deficits.Our data suggest thatincreased COX-2 activity may contribute to proinflammatory responses, including macrophage chemotaxis, during exposure to hyperoxia.Modulation of COX-2 activity may be a useful therapeutic target to limit hyperoxia-induced inflammation in preterm infants at risk of developing BPD.

Original languageEnglish (US)
Pages (from-to)502-511
Number of pages10
JournalFree Radical Biology and Medicine
Volume61
DOIs
StatePublished - Jun 4 2013

Keywords

  • Bronchopulmonary dysplasia
  • Cyclooxygenase-2
  • Hyperoxia
  • Prostaglandins

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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