ANTI-INFLAMMATORY ACTIONS OF CYTOCHROME P450 EPOXYGENASE-DERIVED EICOSANOIDS

摘要

Epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 epoxygenasesthat have vasodilatory properties similar to endothelium-derivedhyperpolarizing factor (EDHF). The cytochrome P450 isoform CYP2J2 was clonedand identified as a source of EETs in human endothelial cells. Physiologicalconcentrations of EETs or overexpression of CYP2J2 decreased cytolcine-inducedendothelial cell adhesion molecule expression and prevented subsequentleukocyte adhesion to the vascular wall by a mechanism involving inhibition oftranscription factor NF-.kappa.B and I.kappa.B kinase (IKK). The inhibitoryeffects of EETs were independent of their membrane hypopolarizing effectssuggesting that these molecules play an important non-vasodilatory role invascular inflammation.