Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Mol Aspects Med. 2018 Dec;64:1-17. doi: 10.1016/j.mam.2017.08.002. Epub 2017 Sep 1.
While protective, the acute inflammatory response when uncontrolled can lead to further tissue damage and chronic inflammation that is now widely recognized to play important roles in many commonly occurring diseases, such as cardiovascular disease, neurodegenerative diseases, metabolic syndrome, and many other diseases of significant public health concern. The ideal response to initial challenges of the host is complete resolution of the acute inflammatory response, which is now recognized to be a biosynthetically active process governed by specialized pro-resolving mediators (SPM). These chemically distinct families include lipoxins, resolvins, protectins and maresins that are biosynthesized from essential fatty acids. The biosynthesis and complete stereochemical assignments of the major SPM are established, and new profiling procedures have recently been introduced to document the activation of these pathways in vivo with isolated cells and in human tissues. The active resolution phase leads to tissue regeneration, where we've recently identified new molecules that communicate during resolution of inflammation to activate tissue regeneration in model organisms. This review presents an update on the documentation of the roles of SPMs and the biosynthesis and structural elucidation of novel mediators that stimulate tissue regeneration, coined conjugates in tissue regeneration. The identification and actions of the three families, maresin conjugates in tissue regeneration (MCTR), protectin conjugates in tissue regeneration (PCTR), and resolvin conjugates in tissue regeneration (RCTR), are reviewed here. The identification, structural elucidation and the pathways and biosynthesis of these new mediators in tissue regeneration demonstrate the host capacity to protect from collateral tissue damage, stimulate clearance of bacteria and debris, and promote tissue regeneration via endogenous pathways and molecules in the resolution metabolome.
虽然具有保护作用，但不受控制的急性炎症反应会导致进一步的组织损伤和慢性炎症，而慢性炎症现在被广泛认为在许多常见疾病中发挥着重要作用，如心血管疾病、神经退行性疾病、代谢综合征和许多其他严重影响公众健康的疾病。宿主对初始挑战的理想反应是完全消除急性炎症反应，现在人们认识到这是一个由专门的促解决介质（SPM）控制的生物合成活性过程。这些化学上不同的家族包括脂氧素、分辨率素、保护素和maresin，它们是由必需脂肪酸生物合成的。主要 SPM 的生物合成和完全立体化学分配已建立，最近引入了新的分析程序来记录这些途径在体内分离细胞和人体组织中的激活情况。主动解决阶段导致组织再生，我们最近在模型生物中发现了在炎症解决过程中传递信息以激活组织再生的新分子。这篇综述介绍了 SPM 的作用以及刺激组织再生的新型介质的生物合成和结构阐明的最新进展，这些新型介质被称为组织再生共轭物。本文综述了maresin 共轭物在组织再生（MCTR）、保护素共轭物在组织再生（PCTR）和分辨率素共轭物在组织再生（RCTR）中的三种家族的鉴定、作用。这些新的组织再生介质的鉴定、结构阐明以及它们在组织再生中的途径和生物合成，证明了宿主有能力通过内源性途径和分辨率代谢物中的分子来保护免受继发组织损伤、刺激清除细菌和碎片以及促进组织再生。
