title: CYP2J2 and EETs protect against lung ischemia/reperfusion injury via anti-inflammatory effects in vivo and in vitro.
abstract: 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 cytochrome 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, including mediators in serum IL-1β, IL-8, TNF-α, 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-κB p65 and degradation of IκBα 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 PPARγ activation.
  
  
  CONCLUSIONS
  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.
authors: Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Wenshu
authors: W
authors: Chen
authors: Shijiang
authors: S
authors: Yang
authors: Wei
authors: W
authors: Ping
authors: Xiangning
authors: X
authors: Fu
authors: Qinzi
authors: Q
authors: Xu
authors: Jianing
authors: J
authors: Wang
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015687:Cell Hypoxia; D002460:Cell Line; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000032:analysis / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects; D019040:E-Selectin / Q000097:blood; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D019007:P-Selectin / Q000097:blood; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000893:Anti-Inflammatory Agents; C000717350:CYP2J2 protein, human; D016207:Cytokines; D019040:E-Selectin; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; C000606204:NFKBIA protein, human; C000606206:Nfkbia protein, rat; D019007:P-Selectin; D047495:PPAR gamma; D051996:Transcription Factor RelA; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2; D015126:8,11,14-Eicosatrienoic Acid