Serhan Charles N
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Annu Rev Immunol. 2007;25:101-37. doi: 10.1146/annurev.immunol.25.022106.141647.
Resolution of inflammation and the return of tissues to homeostasis are essential. Efforts to identify molecular events governing termination of self-limited inflammation uncovered pathways in resolving exudates that actively generate, from essential omega fatty acids, new families of local-acting mediators. These chemical mediator families, termed resolvins and protectins, are potent stereoselective agonists that control the duration and magnitude of inflammation, joining the lipoxins as signals in resolution. This review examines the mapping of these circuits and recent advances in our understanding of the biosynthesis and actions of these novel proresolving lipid mediators. Aspirin jump-starts resolution by triggering biosynthesis of specific epimers of these mediators. In addition to their origins in inflammation resolution, these compounds also display potent protective roles in neural systems, liver, lung, and eye. Given the potent actions of lipoxins, resolvins, and protectins in models of human disease, deficiencies in resolution pathways may contribute to many diseases and offer exciting new potential for therapeutic control via resolution.
炎症的消退以及组织恢复至内稳态至关重要。为确定控制自限性炎症终止的分子事件所做的努力，揭示了在消退性渗出物中起作用的途径，这些途径能从必需的ω脂肪酸中积极生成新的局部作用介质家族。这些化学介质家族，即消退素和保护素，是强效的立体选择性激动剂，可控制炎症的持续时间和程度，与脂氧素一同作为炎症消退的信号。本文综述了这些通路的图谱绘制以及我们对这些新型促消退脂质介质的生物合成和作用理解的最新进展。阿司匹林通过触发这些介质特定差向异构体的生物合成启动炎症消退。除了起源于炎症消退外，这些化合物在神经系统、肝脏、肺和眼睛中也发挥着强大的保护作用。鉴于脂氧素、消退素和保护素在人类疾病模型中的强大作用，消退途径的缺陷可能导致多种疾病，并为通过炎症消退进行治疗控制提供了令人兴奋的新潜力。
