Department of Biochemistry & Pharmacology, Faculty of Medicine, Dentistry and Health Sciences, School of Biomedical Sciences, The University of Melbourne, Parkville, VIC 3010, Australia.
Gut-Axis Injury and Repair Laboratory, Department of Medicine Western Health, Melbourne University, Melbourne, VIC 3021, Australia.
Int J Mol Sci. 2021 Jul 16;22(14):7606. doi: 10.3390/ijms22147606.
Cystic fibrosis (CF) is caused by a defect in the cystic fibrosis transmembrane conductance regulator protein (CFTR) which instigates a myriad of respiratory complications including increased vulnerability to lung infections and lung inflammation. The extensive influx of pro-inflammatory cells and production of mediators into the CF lung leading to lung tissue damage and increased susceptibility to microbial infections, creates a highly inflammatory environment. The CF inflammation is particularly driven by neutrophil infiltration, through the IL-23/17 pathway, and function, through NE, NETosis, and NLRP3-inflammasome formation. Better understanding of these pathways may uncover untapped therapeutic targets, potentially reducing disease burden experienced by CF patients. This review outlines the dysregulated lung inflammatory response in CF, explores the current understanding of CFTR modulators on lung inflammation, and provides context for their potential use as therapeutics for CF. Finally, we discuss the determinants that need to be taken into consideration to understand the exaggerated inflammatory response in the CF lung.
囊性纤维化（CF）是由囊性纤维化跨膜电导调节蛋白（CFTR）的缺陷引起的，这引发了无数的呼吸并发症，包括增加对肺部感染和炎症的易感性。大量促炎细胞和介质涌入 CF 肺部，导致肺组织损伤和增加对微生物感染的易感性，从而产生高度炎症环境。CF 炎症特别由中性粒细胞浸润通过 IL-23/17 途径以及通过 NE、NETosis 和 NLRP3 炎症小体形成来驱动。更好地了解这些途径可能会发现未开发的治疗靶点，从而潜在地减轻 CF 患者的疾病负担。本综述概述了 CF 中失调的肺部炎症反应，探讨了 CFTR 调节剂对肺部炎症的现有认识，并为它们作为 CF 治疗药物的潜在用途提供了背景。最后，我们讨论了理解 CF 肺部过度炎症反应需要考虑的决定因素。
