TY - JOUR
T1 - Cyclooxygenase-2 in newborn hyperoxic lung injury
AU - Britt, Rodney D.
AU - Velten, Markus
AU - Tipple, Trent E.
AU - Nelin, Leif D.
AU - Rogers, Lynette K.
N1 - Funding Information:
The authors thank Dr. Lyn Wanket and Morgan Locy for technical assistance.This work was supported by National Institutes of Health (R.D.B., F31HL097619;T.E.T. , K08HL093365–03 ;and L.K.R., R01AT006880 ) and the Deutsche Forschungsgemeinschaft (M.V., VE 614/1–1 ).
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Bronchopulmonary dysplasia
KW - Cyclooxygenase-2
KW - Hyperoxia
KW - Prostaglandins
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U2 - 10.1016/j.freeradbiomed.2013.04.012
DO - 10.1016/j.freeradbiomed.2013.04.012
M3 - Article
C2 - 23624331
AN - SCOPUS:84878310179
SN - 0891-5849
VL - 61
SP - 502
EP - 511
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -