Dual modulation of cyclooxygenase and CYP epoxygenase metabolism and acute vascular inflammation in mice
| Autor: | Darryl C. Zeldin, Yangmei Deng, Akinyemi Oni-Orisan, Robert N. Schuck, Craig R. Lee, Fred B. Lih, Katherine N. Theken, Matthew L. Edin, Kenneth B. Tomer, Laura M. DeGraff, Kimberly C. Molnar |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
14-Eicosatrienoic Acid Physiology Prostaglandin Indomethacin Pharmacology Medical Biochemistry and Metabolomics Biochemistry Cytochrome P-450 CYP2J2 Transgenic CYP2J2 chemistry.chemical_compound Mice 8 11 14-Eicosatrienoic Acid Cytochrome P-450 Enzyme System 2.1 Biological and endogenous factors Aetiology Lung Vascular inflammation Epoxide Hydrolases biology Eicosanoid metabolism Cyclooxygenase Liver Myeloperoxidase Acute Disease Female medicine.symptom Epoxygenase Biochemistry & Molecular Biology Mice Transgenic Inflammation Epoxyeicosatrienoic acid Article In vivo Vascular medicine Animals Cyclooxygenase Inhibitors Endothelium Peroxidase Cell Biology Endotoxins Soluble epoxide hydrolase chemistry Gene Expression Regulation Prostaglandin-Endoperoxide Synthases biology.protein Endothelium Vascular |
| DOI: | 10.17615/f8bx-6k60 |
| Popis: | Cyclooxygenase (COX)-derived prostaglandins and cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids are important regulators of inflammation; however, functional interactions between these pathways in the regulation of vascular inflammation in vivo have not been studied. We investigated the relative and additive effects of endothelial CYP2J2 overexpression (Tie2-CYP2J2-Tr), global sEH disruption (Ephx2(-/-)), and pharmacologic COX inhibition with indomethacin on the acute vascular inflammatory response to endotoxin in mice. Compared to vehicle-treated wild-type C57BL/6 controls, induction of myeloperoxidase (MPO) activity in lung and liver was similarly attenuated in Tie2-CYP2J2-Tr mice, Ephx2(-/-) mice and wild-type mice treated with moderate dose indomethacin. Dual modulation of both pathways, however, did not produce an additive anti-inflammatory effect. These findings demonstrate that both COX and CYP epoxygenase-mediated eicosanoid metabolism are important regulators of the acute vascular inflammatory response in vivo, and suggest that the anti-inflammatory effects of modulating each pathway may be mediated, at least in part, by overlapping mechanisms. |
| Databáze: | OpenAIRE |
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