Anti-Inflammatory Properties of Cytochrome P450 Epoxygenase-Derived Eicosanoids

• Published in: Science (American Association for the Advancement of Science) 1999-08, Vol.285 (5431), p.1276-1279
• Main Authors: Node, Koichi, Huo, Yuqing, Ruan, Xiulu, Yang, Baichun, Spiecker, Martin, Ley, Klaus, Zeldin, Darryl C., Liao, James K.
• Format: Article
• Language: English
• Subjects: 8,11,14-Eicosatrienoic Acid - analogs & derivatives; 8,11,14-Eicosatrienoic Acid - metabolism; 8,11,14-Eicosatrienoic Acid - pharmacology; Analysis; Animals; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Arachidonic acid; Biological and medical sciences; Carotid arteries; Carotid Arteries - cytology; Cattle; Cell adhesion; Cell Adhesion - drug effects; Cell Adhesion Molecules - biosynthesis; Cells, Cultured; Cellular biology; Cloning; Coronary vessels; Coronary Vessels - enzymology; Cytochrome P-450; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Cytochromes; DNA-Binding Proteins - metabolism; Eicosanoids; Endothelial cells; Endothelium, Vascular - enzymology; Endothelium, Vascular - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Hydroxyeicosatetraenoic Acids - pharmacology; I-kappa B Kinase; I-kappa B Proteins; Inflammation; Inhibition; Mice; Mice, Inbred C57BL; Molecular and cellular biology; Molecular Biology; Molecules; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; Organic pigments; Oxygenases - genetics; Oxygenases - metabolism; Physiological aspects; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - pharmacology; Ungulates; Vascular Cell Adhesion Molecule-1 - biosynthesis; Vascular Cell Adhesion Molecule-1 - genetics
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.285.5431.1276

The epoxyeicosatrienoic acids (EETs) are products of cytochrome P450 epoxygenases that have vasodilatory properties similar to that of endothelium-derived hyperpolarizing factor. The cytochrome P450 isoform CYP2J2 was cloned and identified as a potential source of EETs in human endothelial cells. Physiological concentrations of EETs or overexpression of CYP2J2 decreased cytokine-induced endothelial cell adhesion molecule expression, and EETs prevented leukocyte adhesion to the vascular wall by a mechanism involving inhibition of transcription factor NF-κB and IκB kinase. The inhibitory effects of EETs were independent of their membrane-hyperpolarizing effects, suggesting that these molecules play an important nonvasodilatory role in vascular inflammation.