Hsiao Hsi-Min, Thatcher Thomas H, Colas Romain A, Serhan Charles N, Phipps Richard P, Sime Patricia J
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York.
Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, New York; Division of Pulmonary and Critical Care Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York.
Am J Pathol. 2015 Dec;185(12):3189-201. doi: 10.1016/j.ajpath.2015.08.008. Epub 2015 Oct 24.
Chronic obstructive pulmonary disease is characterized, in part, by chronic inflammation that persists even after smoking cessation, suggesting that a failure to resolve inflammation plays an important role in the pathogenesis of the disease. It is widely recognized that the resolution of inflammation is an active process, governed by specialized proresolving lipid mediators, including lipoxins, resolvins, maresins, and protectins. Here, we report that proresolving signaling and metabolic pathways are disrupted in lung tissue from patients with chronic obstructive pulmonary disease, suggesting that supplementation with proresolving lipid mediators might reduce the development of emphysema by controlling chronic inflammation. Groups of mice were exposed long-term to cigarette smoke and treated with the proresolving mediator resolvin D1. Resolvin D1 was associated with a reduced development of cigarette smoke-induced emphysema and airspace enlargement, with concurrent reductions in inflammation, oxidative stress, and cell death. Interestingly, resolvin D1 did not promote the differentiation of M2 macrophages and did not promote tissue fibrosis. Taken together, our results suggest that cigarette smoking disrupts endogenous proresolving pathways and that supplementation with specialized proresolving lipid mediators is an important therapeutic strategy in chronic lung disease, especially if endogenous specialized proresolving lipid mediator signaling is impaired.
慢性阻塞性肺疾病的部分特征是即使戒烟后仍存在慢性炎症，这表明炎症未能消退在该疾病的发病机制中起重要作用。人们普遍认识到，炎症的消退是一个由包括脂氧素、消退素、马雷素和保护素在内的特异性促消退脂质介质调控的活跃过程。在此，我们报告慢性阻塞性肺疾病患者肺组织中的促消退信号传导和代谢途径受到破坏，这表明补充促消退脂质介质可能通过控制慢性炎症来减少肺气肿的发展。将小鼠分组长期暴露于香烟烟雾中，并给予促消退介质消退素D1进行治疗。消退素D1与香烟烟雾诱导的肺气肿发展和肺泡腔扩大的减轻相关，同时炎症、氧化应激和细胞死亡也减少。有趣的是，消退素D1并未促进M2巨噬细胞的分化，也未促进组织纤维化。综上所述，我们的结果表明吸烟会破坏内源性促消退途径，补充特异性促消退脂质介质是慢性肺病的一种重要治疗策略，尤其是在内源性特异性促消退脂质介质信号受损的情况下。
