Journal
FASEB JOURNAL
Volume 28, Issue 2, Pages 586-593Publisher
WILEY
DOI: 10.1096/fj.13-236224
Keywords
bioactive lipid; metabolomics
Categories
Funding
- Japanese Science and Technology Agency Precursory Research for Embryonic Science and Technology (PRESTO)
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- program for Promotion of Basic and Applied Research for Innovations in Bio-Oriented industry
- Grants-in-Aid for Scientific Research [26102716, 26253003, 22116006, 25460007, 23227004] Funding Source: KAKEN
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Eicosapentaenoic acid (EPA) has beneficial effects in many inflammatory disorders. In this study, dietary EPA was converted to 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) by -3 epoxygenation in the mouse peritoneal cavity. Mediator lipidomics revealed a series of novel oxygenated metabolites of 17,18-EpETE, and one of the major metabolites, 12-hydroxy-17,18-epoxyeicosatetraenoic acid (12-OH-17,18-EpETE), displayed a potent anti-inflammatory action by limiting neutrophil infiltration in murine zymosan-induced peritonitis. 12-OH-17,18-EpETE inhibited leukotriene B-4-induced neutrophil chemotaxis and polarization in vitro in a low nanomolar range (EC50 0.6 nM). The complete structures of two natural isomers were assigned as 12S-OH-17R,18S-EpETE and 12S-OH-17S,18R-EpETE, using chemically synthesized stereoisomers. These natural isomers displayed potent anti-inflammatory action, whereas the unnatural stereoisomers were essentially devoid of activity. These results demonstrate that 17,18-EpETE derived from dietary EPA is converted to a potent bioactive metabolite 12-OH-17,18-EpETE, which may generate an endogenous anti-inflammatory metabolic pathway.Kubota, T., Arita, M., Isobe, Y., Iwamoto, R., Goto, T., Yoshioka, T., Urabe, D., Inoue, M., Arai, H. Eicosapentaenoic acid is converted via -3 epoxygenation to the anti-inflammatory metabolite 12-hydroxy-17,18-epoxyeicosatetraenoic acid.
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