Resolvin E2: Identification and anti-inflammatory actions: Pivotal role of human 5-lipoxygenase in resolvin E series biosynthesis
Resolvin E2: Identification and anti-inflammatory actions: Pivotal role of human 5-lipoxygenase in resolvin E series biosynthesis
复制标题
DOI：
10.1016/j.chembiol.2006.09.011
复制
发表时间：
2006-11-01
影响因子：
--
通讯作者：
Serhan, Charles N.
中科院分区：
文献类型：
--
作者：
Tjonahen, Eric;Oh, Sungwhan F.;Serhan, Charles N.
该家族由omega-3脂肪酸衍生的介体组成，包括由二十碳五烯酸(EPA)产生的E系列溶栓，具有强大的抗炎特性。本文报道了解决素E_2(RvE_2)的分离、鉴定及其生物活性。在小鼠腹膜炎模型中，RvE2可阻止酵母多糖诱导的中性粒细胞(PMN)白细胞的浸润，并显示出有效的抗炎作用。我们还证明了人重组5-脂氧合酶由E系列解析素的一个共同前体，即18-羟基二十碳五烯酸酯(18-HEPE)产生RvE2。此外，在RvE1地层中，最初的5-过氧化氢中间体也被转化为5(6)-环氧化物中间体。这些结果表明，RvE2和RvE1可能有助于omega-3脂肪酸在人类疾病中的有益作用。此外，他们还表明，人类白细胞中的5-脂氧合酶是一种关键酶，可以产生促炎和抗炎化学介质。
The family of resolvins consists of omega-3 fatty acid-derived mediators, including E series resolvins generated from eicosapentaenoic acid (EPA), and carry potent anti-inflammatory properties. Here, we report the isolation, identification, and bioactions of resolvin E2 (RvE2), which is 5S,18-dihydroxy-eicosapentaenoic acid. RvE2 stopped zymosan-induced polymorphonuclear (PMN) leukocyte infiltration and displayed potent anti-inflammatory properties in murine peritonitis. We also demonstrate that human recombinant 5-lipoxygenase generates RvE2 from a common precursor of E series resolvins, namely, 18-hydroxyeicosapentaenoate (18-HEPE). Furthermore, the initial 5-hydroperoxide intermediate was also converted to a 5(6)-epoxide intermediate in RvE1 formation. These results demonstrate that RvE2, together with RvE1, may contribute to the beneficial actions of omega-3 fatty acids in human diseases. Moreover, they indicate that the 5-lipoxygenase in human leukocytes is a pivotal enzyme that can produce both pro- and anti-inflammatory chemical mediators.