Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids.
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-kappaB and IkappaB 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.
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Vascular Medicine and Atherosclerosis Unit, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, LMRC-322, Boston, MA 02115, USA.
Huo
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Ruan
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Yang
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B
Spiecker
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Ley
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Zeldin
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DC
Liao
J K
JK
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology; D002339:Carotid Arteries / Q000166:cytology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000201:enzymology; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; C000717350:CYP2J2 protein, human; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D006893:Hydroxyeicosatetraenoic Acids; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; C040776:5,6-epoxy-8,11,14-eicosatrienoic acid; C050715:8,9-epoxyeicosatrienoic acid; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000090762:Cytochrome P-450 CYP2J2; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; D015126:8,11,14-Eicosatrienoic Acid