Serhan C N
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
J Thromb Haemost. 2009 Jul;7 Suppl 1:44-8. doi: 10.1111/j.1538-7836.2009.03396.x.
Using a systems approach to profile self-limited inflammatory exudates, we identified three novel families of lipid-derived mediators, coined the resolvins, protectins and most recently, the maresins that control both the magnitude and duration of inflammation. The mapping of these endogenous resolution circuits provides new avenues to probe the molecular basis of many widely occurring inflammatory diseases. This article focuses on our recent advances on the functional metabolomics of this novel genus of specialized pro-resolving mediators (SPM). SPM include resolvins, protectins and maresins and are biosynthesized from essential omega-3 fatty acid precursors. Each possesses potent multi-pronged actions that proved to be stereoselective with human cells and in animal disease models. Resolvins and protectins are also produced in bone marrow. Together, these findings suggest that defective resolution mechanism(s) may underlie some chronic inflammatory diseases. Moreover, identification of functional SPM biosynthesized during inflammation-resolution indicates that resolution is an active process.
通过采用系统方法来剖析自限性炎性渗出物,我们鉴定出了三个新的脂质衍生介质家族,即消退素、保护素,以及最近发现的maresin,它们可控制炎症的程度和持续时间。这些内源性消退回路的图谱绘制为探究许多广泛存在的炎性疾病的分子基础提供了新途径。本文重点介绍我们在这种新型特殊促消退介质(SPM)功能代谢组学方面的最新进展。SPM包括消退素、保护素和maresin,由必需的ω-3脂肪酸前体生物合成。每种介质都具有强大的多方面作用,在人类细胞和动物疾病模型中显示出立体选择性。消退素和保护素也在骨髓中产生。这些发现共同表明,缺陷的消退机制可能是某些慢性炎性疾病的基础。此外,对炎症消退过程中生物合成的功能性SPM的鉴定表明,消退是一个活跃的过程。