Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids

The epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 epoxy- genases that have vasodilatory properties similar to that of endothelium-de rived hyperpolarizing factor. The cytochrome P450 isoform CYP2J2 was cloned and identified as a potential source of EETs in human endothelial cells. P hysiological concentrations of EETs or overexpression of CYP2J2 decreased c ytokine-induced endothelial cell adhesion molecule expression, and EETs pre vented leukocyte adhesion to the vascular wall by a mechanism involving inh ibition of transcription factor NF-kappa B and I kappa B kinase. The inhibi tory effects of EETs were independent of their membrane-hyperpolarizing eff ects, suggesting that these molecules play an important nonvasodilatory rol e in vascular inflammation.