Identification and Structure Determination of Novel Anti-inflammatory Mediator Resolvin E3, 17,18-Dihydroxyeicosapentaenoic Acid

被引：191

作者：

Isobe, Yosuke ^{[1
,3
]}

Arita, Makoto ^{[1
,6
]}

Matsueda, Shinnosuke ^{[1
]}

Iwamoto, Ryo ^{[3
]}

Fujihara, Takuji ^{[3
,5
]}

Nakanishi, Hiroki ^{[4
]}

Taguchi, Ryo ^{[4
]}

Masuda, Koji ^{[3
,5
]}

Sasaki, Kenji ^{[2
]}

Urabe, Daisuke ^{[2
]}

Inoue, Masayuki ^{[2
]}

Arai, Hiroyuki ^{[1
]}

机构：

[1] Univ Tokyo, Dept Hlth Chem, Bunkyo Ku, Tokyo 1130033, Japan

[2] Univ Tokyo, Dept Integral Analyt Chem, Bunkyo Ku, Tokyo 1130033, Japan

[3] Univ Tokyo, Grad Sch Pharmaceut Sci, Business Acad Collaborat Lab, Bunkyo Ku, Tokyo 1130033, Japan

[4] Univ Tokyo, Grad Sch Med, Dept Metabolome, Bunkyo Ku, Tokyo 1130033, Japan

[5] Shionogi Res Labs, Toyonaka, Osaka 5610825, Japan

[6] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama, Japan

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2012年 / 287卷 / 13期

基金：

日本科学技术振兴机构;

关键词：

LIPID MEDIATORS; FATTY-ACIDS; INFLAMMATION; RESOLUTION; OMEGA-3-FATTY-ACIDS; BIOSYNTHESIS; PRODUCTS; ASPIRIN; FAMILY; N-3;

D O I：

10.1074/jbc.M112.340612

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Bioactive mediators derived from omega-3 eicosapentaenoic acid (EPA) elicit potent anti-inflammatory actions. Here, we identified novel EPA metabolites, including 8,18-dihydroxyei-cosapentaenoic acid (8,18-diHEPE), 11,18-diHEPE, 12,18-diHEPE, 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.

引用

页码：10525 / 10534

页数：10

共 27 条

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