Cyclooxygenase-2 in newborn hyperoxic lung injury.
Cyclooxygenase-2 in newborn hyperoxic lung injury.
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DOI：
10.1016/j.freeradbiomed.2013.04.012
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发表时间：
2013-08
影响因子：
7.4
通讯作者：
Rogers, Lynette K.
中科院分区：
文献类型：
--
作者：
Britt, Rodney D., Jr.;Velten, Markus;Tipple, Trent E.;Nelin, Leif D.;Rogers, Lynette K.
超生理氧浓度，机械通气和炎症显著促进支气管肺发育不良（BPD）的发展。新生小鼠暴露于高氧环境中会引起炎症和肺泡受损，这与BPD婴儿的情况类似。先前，我们证明了高氧暴露的新生小鼠肺环氧化酶-2 （COX-2）蛋白表达增加。本研究旨在确定COX-2在新生儿高氧肺损伤中的作用。我们验证了COX-2活性的衰减可以减少高氧诱导的炎症和改善肺泡化的假设。新生C3H/HeN小鼠在出生后的前7天每天注射载体、阿司匹林（非选择性COX-2抑制剂）或塞来昔布（选择性COX-2抑制剂）。其他研究使用野生型（C57Bl/6, COX-2+/+），杂合子（COX-2+/−）和纯合子（COX-2−/−）转基因小鼠。小鼠暴露在室内空气（21% O2）或高氧（85% O2）中14天。注射阿司匹林和COX-2 - / -幼崽支气管肺泡灌洗液（BAL）中单核细胞趋化蛋白（MCP-1）水平降低。阿司匹林和塞来昔布治疗均可减少肺泡壁和空气中的巨噬细胞数量。阿司匹林和塞来昔布治疗可减弱高氧诱导的COX活性，包括前列腺素（PG）D2代谢物水平的改变。然而，COX活性降低并不能预防高氧诱导的肺发育缺陷。我们的数据表明，在暴露于高氧环境时，COX-2活性的增加可能有助于促炎反应，包括巨噬细胞趋化性。调节COX-2活性可能是一个有用的治疗靶点，以限制高氧诱导的炎症在早产儿发展成BPD的风险。
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 mice were injected daily with vehicle, aspirin (non-selective 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. Mice were 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 airspaces. 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 suggests that increased COX-2 activity may contribute to pro-inflammatory 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.
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DOI：
10.4049/jimmunol.1101873
发表时间：
2012-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Church RJ;Jania LA;Koller BH
通讯作者：
Koller BH
影响因子：
2.9
作者：
Loftin, CD;Tiano, HF;Langenbach, R
通讯作者：
Langenbach, R
DOI：
10.1084/jem.20022218
发表时间：
2003-08-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Honda K;Arima M;Cheng G;Taki S;Hirata H;Eda F;Fukushima F;Yamaguchi B;Hatano M;Tokuhisa T;Fukuda T
通讯作者：
Fukuda T
影响因子：
3.6
作者：
Jobe AH
通讯作者：
Jobe AH
DOI：
10.1084/jem.193.2.255
发表时间：
2001-01-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hirai H;Tanaka K;Yoshie O;Ogawa K;Kenmotsu K;Takamori Y;Ichimasa M;Sugamura K;Nakamura M;Takano S;Nagata K
通讯作者：
Nagata K