Identification and structure determination of novel anti-inflammatory mediator resolvin E3, 17,18-dihydroxyeicosapentaenoic acid

Yosuke Isobe, Makoto Arita, Shinnosuke Matsueda, Ryo Iwamoto, Takuji Fujihara, Hiroki Nakanishi, Ryo Taguchi, Koji Masuda, Kenji Sasaki, Daisuke Urabe, Masayuki Inoue, Hiroyuki Arai

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Bioactive mediators derived from omega-3 eicosapentaenoic acid (EPA) elicit potent anti-inflammatory actions. Here, we identified novel EPA metabolites, including 8,18-dihydroxyeicosapentaenoic acid (8,18-diHEPE), 11,18-diHEPE, 12,18-di- HEPE, and 17,18-diHEPE from 18-HEPE. Unlike resolvins E1 and E2, both of which are biosynthesized by neutrophils via the 5-lipoxygenase pathway, these metabolites are biosynthesized by eosinophils via the 12/15-lipoxygenase pathway. Among them, two stereoisomers of 17,18-diHEPE, collectively termed resolvin E3 (RvE3), displayed a potent anti-inflammatory action by limiting neutrophil infiltration in zymosan-induced peritonitis. The planar structure of RvE3 was unambiguously determined to be 17,18-dihydroxy-5Z,8Z,11Z,13E,15E-EPE by high resolution NMR, and the two stereoisomers were assigned to have 17,18R- and 17,18S-dihydroxy groups, respectively, using chemically synthesized 18R- and 18S-HEPE as precursors. Both 18R- and 18S-RvE3 inhibited neutrophil chemotaxis in vitro at low nanomolar concentrations. These findings suggest that RvE3 contributes to the beneficial actions of EPA in controlling inflammation and related diseases.

Original languageEnglish
Pages (from-to)10525-10534
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number13
DOIs
Publication statusPublished - 2012 Mar 23
Externally publishedYes

Fingerprint

Eicosapentaenoic Acid
Anti-Inflammatory Agents
Stereoisomerism
Metabolites
Neutrophils
Arachidonate 5-Lipoxygenase
Zymosan
Neutrophil Infiltration
Chemotaxis
Peritonitis
Infiltration
Eosinophils
Nuclear magnetic resonance
Inflammation
Acids
17,18-dihydroxyeicosapentaenoic acid

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Identification and structure determination of novel anti-inflammatory mediator resolvin E3, 17,18-dihydroxyeicosapentaenoic acid. / Isobe, Yosuke; Arita, Makoto; Matsueda, Shinnosuke; Iwamoto, Ryo; Fujihara, Takuji; Nakanishi, Hiroki; Taguchi, Ryo; Masuda, Koji; Sasaki, Kenji; Urabe, Daisuke; Inoue, Masayuki; Arai, Hiroyuki.

In: Journal of Biological Chemistry, Vol. 287, No. 13, 23.03.2012, p. 10525-10534.

Research output: Contribution to journalArticle

Isobe, Y, Arita, M, Matsueda, S, Iwamoto, R, Fujihara, T, Nakanishi, H, Taguchi, R, Masuda, K, Sasaki, K, Urabe, D, Inoue, M & Arai, H 2012, 'Identification and structure determination of novel anti-inflammatory mediator resolvin E3, 17,18-dihydroxyeicosapentaenoic acid', Journal of Biological Chemistry, vol. 287, no. 13, pp. 10525-10534. https://doi.org/10.1074/jbc.M112.340612
Isobe, Yosuke ; Arita, Makoto ; Matsueda, Shinnosuke ; Iwamoto, Ryo ; Fujihara, Takuji ; Nakanishi, Hiroki ; Taguchi, Ryo ; Masuda, Koji ; Sasaki, Kenji ; Urabe, Daisuke ; Inoue, Masayuki ; Arai, Hiroyuki. / Identification and structure determination of novel anti-inflammatory mediator resolvin E3, 17,18-dihydroxyeicosapentaenoic acid. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 13. pp. 10525-10534.
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