Identification and characterization of novel omega-3 polyunsaturated fatty acid-derived mediator with anti-inflammatory property

具有抗炎特性的新型 omega-3 多不饱和脂肪酸衍生介质的鉴定和表征

• 批准号: 21370051
• 负责人: ARITA Makoto
• 金额: $ 12.06万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21370051/
• 关键词: ホルモンと生理活性物質; ω3脂肪酸; 抗炎症作用; メタボロミクス; 生理活性脂質

In this study, we identified a novel omega-3 polyunsaturated fatty acid-derived anti-inflammatory mediator 17, 18-diHEPE, termed resolvin E3(RvE3). The chemical structure of RvE3 was determined by LC-MS/MS-based lipidomics, stereoselective organic synthesis, and high-resolution NMR. Unlike previously identified RvE1 and RvE2, both of which are biosynthesized by neutrophils via 5-LOX pathway, RvE3 was biosynthesized by eosinophils via 12/15-LOX pathway. RvE3 at nanogram dosages displayed a potent anti-inflammatory action in vivo by limiting neutrophil infiltration in zymosan-induced peritonitis. These findings propose a novel metabolic cascade for the beneficial actions of omega-3 fatty acid in controlling inflammation and related diseases

在这项研究中，我们鉴定了一种新型 omega-3 多不饱和脂肪酸衍生的抗炎介质 17, 18-diHEPE，称为 resolvin E3(RvE3)。 RvE3 的化学结构通过基于 LC-MS/MS 的脂质组学、立体选择性有机合成和高分辨率 NMR 确定。与之前鉴定的 RvE1 和 RvE2 不同，RvE1 和 RvE2 均由中性粒细胞通过 5-LOX 途径生物合成，RvE3 是由嗜酸性粒细胞通过 12/15-LOX 途径生物合成。纳克剂量的 RvE3 通过限制酵母聚糖诱导的腹膜炎中的中性粒细胞浸润，在体内表现出有效的抗炎作用。这些发现提出了 omega-3 脂肪酸在控制炎症和相关疾病方面的有益作用的新型代谢级联

项目成果

Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium-induced colitis.

• DOI: 10.1002/ibd.21029
• 发表时间: 2010-01
• 期刊: INFLAMMATORY BOWEL DISEASES
• 影响因子: 4.9
• 作者: Ishida, Tsukasa;Yoshida, Masaru;Arita, Makoto;Nishitani, Yosuke;Nishiumi, Shin;Masuda, Atsuhiro;Mizuno, Shigeto;Takagawa, Tetsuya;Morita, Yoshinori;Kutsumi, Hiromu;Inokuchi, Hideto;Serhan, Charles N.;Blumberg, Richard S.;Azuma, Takeshi
• 通讯作者: Azuma, Takeshi

Resolvins as regulators of the immune system.

• DOI: 10.1100/tsw.2010.72
• 发表时间: 2010-05-04
• 期刊: TheScientificWorldJournal
• 作者: Seki H;Sasaki T;Ueda T;Arita M
• 通讯作者: Arita M

Metabolomics of polyunsaturated fatty acid-derived mediators in inflam mation and resolution

多不饱和脂肪酸衍生介质在炎症和消退中的代谢组学

• 发表时间: 2010
• 作者: M. Hirano;B. Y. Ma;N. Kawasaki;S. Oka;and T. Kawasaki;Makoto Arita
• 通讯作者: Makoto Arita

Novel role of eosinophils in controlling the resolution of acute inflammation by producing pro-resolving lipid mediators

嗜酸性粒细胞通过产生促消退脂质介质在控制急性炎症消退中的新作用

• 发表时间: 2011
• 作者: 堀越正美;Mamoru Sato;Kouhei Matsuda;有田誠;堀越正美;Mamoru Sato;有田誠;松田恒平;佐藤衛;Makoto Arita
• 通讯作者: Makoto Arita

Eosinophils contribute to the resolution of acute peritonitis by producing pro-resolving lipid mediators

嗜酸性粒细胞通过产生促消退脂质介质来促进急性腹膜炎的消退

• 发表时间: 2011
• 作者: 小島健史;島倉征一;中町智哉;影山晴秋;内山実;高橋明義;塩田清二;松田恒平;Makoto Arita
• 通讯作者: Makoto Arita