Eicosapentaenoic acid is converted via ω-3 epoxygenation to the anti-inflammatory metabolite 12-hydroxy-17,18-epoxyeicosatetraenoic acid

Tadafumi Kubota, Makoto Arita, Yosuke Isobe, Ryo Iwamoto, Tomomi Goto, Takeshi Yoshioka, Daisuke Urabe, Masayuki Inoue, Hiroyuki Arai

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 ω-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 B4-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,18REpETE, 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.

Original languageEnglish
Pages (from-to)586-593
Number of pages8
JournalFASEB Journal
Volume28
Issue number2
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Eicosapentaenoic Acid
Metabolites
Anti-Inflammatory Agents
Acids
Stereoisomerism
Isomers
Zymosan
Leukotriene B4
Neutrophil Infiltration
Peritoneal Cavity
Chemotaxis
Metabolic Networks and Pathways
Peritonitis
Infiltration
17,18-epoxy-5,8,11,14-eicosatetraenoic acid
Neutrophils
hydroxide ion
Polarization

Keywords

  • Bioactive lipid
  • Metabolomics

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

Eicosapentaenoic acid is converted via ω-3 epoxygenation to the anti-inflammatory metabolite 12-hydroxy-17,18-epoxyeicosatetraenoic acid. / Kubota, Tadafumi; Arita, Makoto; Isobe, Yosuke; Iwamoto, Ryo; Goto, Tomomi; Yoshioka, Takeshi; Urabe, Daisuke; Inoue, Masayuki; Arai, Hiroyuki.

In: FASEB Journal, Vol. 28, No. 2, 2014, p. 586-593.

Research output: Contribution to journalArticle

Kubota, Tadafumi ; Arita, Makoto ; Isobe, Yosuke ; Iwamoto, Ryo ; Goto, Tomomi ; Yoshioka, Takeshi ; Urabe, Daisuke ; Inoue, Masayuki ; Arai, Hiroyuki. / Eicosapentaenoic acid is converted via ω-3 epoxygenation to the anti-inflammatory metabolite 12-hydroxy-17,18-epoxyeicosatetraenoic acid. In: FASEB Journal. 2014 ; Vol. 28, No. 2. pp. 586-593.
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