Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 35, Issue 5, Pages 2043-2054Publisher
KARGER
DOI: 10.1159/000374011
Keywords
Cytochrome P450 epoxygenase 2J2; Epoxyeicosatrienoic acid; Lung ischemia/reperfusion injury; Inflammation
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Funding
- National Natural Science Foundation of China [81000031]
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Background: Injurious inflammatory response is critical to the development of lung ischemia/reperfusion injury (LIRI). The cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), which exert an anti-inflammatory effect on the cardiovascular system. We therefore hypothesized that CYP2J2 overexpression and pretreatment with exogenous EETs may have the potential to reduce LIRI. Methods: A rat model was used to mimic the condition of LIRI by clamping the left pulmonary hilum for 60 minutes, followed by reperfusion for 2 hours. Moreover, we developed a cell model using human pulmonary artery endothelial cells by anoxia for 8 hours, followed by reoxygenation for 16 hours to determine the anti-inflammatory effect and mechanism of CYP2J2 overexpression and exogenous 11,12-EET. Results: Lung ischemia/reperfusion increased lung wet/dry and lung weight/body weight ratios, protein concentration in bronchoalveolar lavage fluid and concentrations of pro-inflammatory mediators in serum, including IL-1 beta, IL-8, TNF-alpha, sP- and sE-selectin, and decreased concentration of anti-inflammatory mediator IL-10. Ischemia/reperfusion also leaded to pulmonary edema and inflammation under light microscopy. Furthermore, activation of NF-kappa B p65 and degradation of I kappa B alpha were remarkably increased in ischemia/reperfusion lung tissues. While CYP2J2 overexpression significantly inhibited the above effects (p<0.05). In vitro data further confirmed the anti-inflammatory effect of CYP2J2 overexpression and 11,12-EET, an effect that may probably be mediated by PPAR gamma activation. Conclusion: CYP2J2 overexpression and administration of exogenous EETs can protect against LIRI via anti-inflammatory effects. This can be a novel potential strategy for prevention and treatment of LIRI. Copyright (C) 2015 S. Karger AG, Basel
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