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Publication : Dual modulation of cyclooxygenase and CYP epoxygenase metabolism and acute vascular inflammation in mice.

First Author  Oni-Orisan A Year  2013
Journal  Prostaglandins Other Lipid Mediat Volume  104-105
Pages  67-73 PubMed ID  23000418
Mgi Jnum  J:327210 Mgi Id  MGI:7328878
Doi  10.1016/j.prostaglandins.2012.09.003 Citation  Oni-Orisan A, et al. (2013) Dual modulation of cyclooxygenase and CYP epoxygenase metabolism and acute vascular inflammation in mice. Prostaglandins Other Lipid Mediat 104-105:67-73
abstractText  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.
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