a Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine , Weill Cornell Medical College , New York , NY , USA.
b New York-Presbyterian Hospital , New York , NY , USA.
Autophagy. 2018;14(2):221-232. doi: 10.1080/15548627.2017.1389823. Epub 2018 Feb 8.
Persistent inflammation within the respiratory tract underlies the pathogenesis of numerous chronic pulmonary diseases including chronic obstructive pulmonary disease, asthma and pulmonary fibrosis. Chronic inflammation in the lung may arise from a combination of genetic susceptibility and environmental influences, including exposure to microbes, particles from the atmosphere, irritants, pollutants, allergens, and toxic molecules. To this end, an immediate, strong, and highly regulated inflammatory defense mechanism is needed for the successful maintenance of homeostasis within the respiratory system. Macroautophagy/autophagy plays an essential role in the inflammatory response of the lung to infection and stress. At baseline, autophagy may be critical for inhibiting spontaneous pulmonary inflammation and fundamental for the response of pulmonary leukocytes to infection; however, when not regulated, persistent or inefficient autophagy may be detrimental to lung epithelial cells, promoting lung injury. This perspective will discuss the role of autophagy in driving and regulating inflammatory responses of the lung in chronic lung diseases with a focus on potential avenues for therapeutic targeting. Abbreviations AR allergic rhinitis AM alveolar macrophage ATG autophagy-related CF cystic fibrosis CFTR cystic fibrosis transmembrane conductance regulator COPD chronic obstructive pulmonary disease CS cigarette smoke CSE cigarette smoke extract DC dendritic cell IH intermittent hypoxia IPF idiopathic pulmonary fibrosis ILD interstitial lung disease MAP1LC3B microtubule associated protein 1 light chain 3 beta MTB Mycobacterium tuberculosis MTOR mechanistic target of rapamycin kinase NET neutrophil extracellular traps OSA obstructive sleep apnea PAH pulmonary arterial hypertension PH pulmonary hypertension ROS reactive oxygen species TGFB1 transforming growth factor beta 1 TNF tumor necrosis factor.
呼吸道内持续存在的炎症是许多慢性肺部疾病（包括慢性阻塞性肺疾病、哮喘和肺纤维化）发病机制的基础。肺部慢性炎症可能是遗传易感性和环境影响（包括暴露于微生物、大气颗粒、刺激物、污染物、过敏原和有毒分子）共同作用的结果。为此，呼吸系统需要一种即时、强烈和高度调节的炎症防御机制，以成功维持内环境稳定。巨自噬/自噬在肺部对感染和应激的炎症反应中起着至关重要的作用。在基础状态下，自噬可能对抑制自发性肺部炎症至关重要，也是肺部白细胞对感染反应的基础；然而，当自噬不受调节时，持续或低效的自噬可能对肺上皮细胞有害，促进肺损伤。本观点将讨论自噬在驱动和调节慢性肺部疾病肺部炎症反应中的作用，重点讨论潜在的治疗靶点途径。缩写词 AR 变应性鼻炎 AM 肺泡巨噬细胞 ATG 自噬相关 CF 囊性纤维化 CFTR 囊性纤维化跨膜电导调节因子 COPD 慢性阻塞性肺疾病 CS 香烟烟雾 CSE 香烟烟雾提取物 DC 树突状细胞 IH 间歇性低氧 IPF 特发性肺纤维化 ILD 间质性肺病 MAP1LC3B 微管相关蛋白 1 轻链 3 结合蛋白 MTB 结核分枝杆菌 MTOR 雷帕霉素靶蛋白激酶 NET 中性粒细胞胞外陷阱 OSA 阻塞性睡眠呼吸暂停 PAH 肺动脉高压 PH 肺动脉高压 ROS 活性氧 TGFB1 转化生长因子β 1 TNF 肿瘤坏死因子。
