title: Cyclooxygenase-2 in newborn hyperoxic lung injury.
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.
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA.
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Britt
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Rheinische Friedrich-Wilhlems-University, University Medical Center, Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Velten
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA; Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43215, USA.
authors.forename: Trent E
authors.initials: TE
authors.lastname: Tipple
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA; Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43215, USA.
authors.forename: Leif D
authors.initials: LD
authors.lastname: Nelin
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA; Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43215, USA. Electronic address: Lynette.Rogers@NationwideChildrens.org.
authors.forename: Lynette K
authors.initials: LK
authors.lastname: Rogers
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D051546:Cyclooxygenase 2 / Q000502:physiology*; D018496:Hyperoxia / Q000150:complications*; D019746:Intramolecular Oxidoreductases / Q000032:analysis; D054834:Lipocalins / Q000032:analysis; D055370:Lung Injury / Q000209:etiology*; D051379:Mice; D008809:Mice, Inbred C3H; D000071876:Prostaglandin-E Synthases
chemical_list: D054834:Lipocalins; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D000071876:Prostaglandin-E Synthases
keywords: Bronchopulmonary dysplasia; Cyclooxygenase-2; Hyperoxia; Prostaglandins