期刊
PROSTAGLANDINS & OTHER LIPID MEDIATORS
卷 104, 期 -, 页码 67-73出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.prostaglandins.2012.09.003
关键词
CYP2J2; Soluble epoxide hydrolase; Cyclooxygenase; Vascular inflammation; Epoxyeicosatrienoic acid; Prostaglandin
资金
- University of North Carolina at Chapel Hill Royster Society of Fellows Chancellor's Fellowship
- American Heart Association [T32 HL069768]
- American Foundation for Pharmaceutical Education
- Intramural Research Program of the NIH/NIEHS [Z01 ES050167, Z01 ES025034]
- [R01 GM088199]
- [R01 GM088199-S1]
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. (C) 2012 Elsevier Inc. All rights reserved.
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