Duvall Melody G, Levy Bruce D
Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Eur J Pharmacol. 2016 Aug 15;785:144-155. doi: 10.1016/j.ejphar.2015.11.001. Epub 2015 Nov 3.
Essential fatty acids can serve as important regulators of inflammation. A new window into mechanisms for the resolution of inflammation was opened with the identification and structural elucidation of mediators derived from these fatty acids with pro-resolving capacity. Inflammation is necessary to ensure the continued health of the organism after an insult or injury; however, unrestrained inflammation can lead to injury "from within" and chronic changes that may prove both morbid and fatal. The resolution phase of inflammation, once thought to be a passive event, is now known to be a highly regulated, active, and complex program that terminates the inflammatory response once the threat has been contained. Specialized pro-resolving mediators (SPMs) are biosynthesized from omega-3 essential fatty acids to resolvins, protectins, and maresins and from omega-6 fatty acids to lipoxins. Through cell-specific actions mediated through select receptors, these SPMs are potent regulators of neutrophil infiltration, cytokine and chemokine production, and clearance of apoptotic neutrophils by macrophages, promoting a return to tissue homeostasis. This process appears to be defective in several common human lung diseases, such as asthma and COPD, which are characterized by chronic unrestrained inflammation and significant associated morbidity. Here, we highlight translational research in animal models of disease and with human subjects that sheds light on this rapidly evolving area of science and review the molecular and cellular components of the resolution of lung inflammation.
必需脂肪酸可作为炎症的重要调节因子。随着具有促炎症消退能力的源自这些脂肪酸的介质的鉴定和结构阐明，开启了一扇了解炎症消退机制的新窗口。炎症对于确保机体在受到损伤或伤害后持续保持健康是必要的；然而，不受控制的炎症会导致“自身”损伤以及可能导致病态和致命的慢性变化。炎症的消退阶段，曾被认为是一个被动过程，现在已知是一个高度调控、活跃且复杂的程序，一旦威胁得到控制，就会终止炎症反应。专门的促炎症消退介质（SPM）由ω-3必需脂肪酸生物合成生成消退素、保护素和促巨噬细胞活化脂介质，由ω-6脂肪酸生物合成生成脂氧素。通过由特定受体介导的细胞特异性作用，这些SPM是中性粒细胞浸润、细胞因子和趋化因子产生以及巨噬细胞清除凋亡中性粒细胞的有效调节因子，促进恢复组织稳态。在几种常见的人类肺部疾病中，如哮喘和慢性阻塞性肺疾病（COPD），这一过程似乎存在缺陷，这些疾病的特征是慢性不受控制的炎症以及显著的相关发病率。在此，我们重点介绍在疾病动物模型和人类受试者中开展的转化研究，这些研究揭示了这一快速发展的科学领域，并综述了肺部炎症消退的分子和细胞成分。
