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特殊促消退介质在囊性纤维化气道疾病中的作用

The Role of Specialized Pro-Resolving Mediators in Cystic Fibrosis Airways Disease.

作者信息

Briottet Maelle, Shum Mickael, Urbach Valerie

机构信息

Institut national de la santé et de la recherche médicale (Inserm) U955, Institut Mondor de Recherche Biomédicale (IMRB), Créteil, France.

出版信息

Front Pharmacol. 2020 Sep 2;11:1290. doi: 10.3389/fphar.2020.01290. eCollection 2020.

Abstract

Cystic Fibrosis (CF) is a recessive genetic disease due to mutations of the Cystic Fibrosis Transmembrane Conductance Regulator () gene encoding the CFTR chloride channel. The ion transport abnormalities related to mutation generate a dehydrated airway surface liquid (ASL) layer, which is responsible for an altered mucociliary clearance, favors infections and persistent inflammation that lead to progressive lung destruction and respiratory failure. The inflammatory response is normally followed by an active resolution phase to return to tissue homeostasis, which involves specialized pro-resolving mediators (SPMs). SPMs promote resolution of inflammation, clearance of microbes, tissue regeneration and reduce pain, but do not evoke unwanted immunosuppression. The airways of CF patients showed a decreased production of SPMs even in the absence of pathogens. SPMs levels in the airway correlated with CF patients' lung function. The prognosis for CF has greatly improved but there remains a critical need for more effective treatments that prevent excessive inflammation, lung damage, and declining pulmonary function for all CF patients. This review aims to highlight the recent understanding of CF airway inflammation and the possible impact of SPMs on functions that are altered in CF airways.

摘要

囊性纤维化(CF)是一种隐性遗传疾病,由编码囊性纤维化跨膜传导调节因子(CFTR)氯离子通道的基因发生突变所致。与CFTR突变相关的离子转运异常会产生脱水的气道表面液体(ASL)层,这会导致黏液纤毛清除功能改变,助长感染和持续性炎症,进而导致进行性肺破坏和呼吸衰竭。炎症反应通常会继之以一个活跃的消退阶段,以恢复组织稳态,这涉及特殊的促消退介质(SPMs)。SPMs可促进炎症消退、清除微生物、促进组织再生并减轻疼痛,但不会引起不必要的免疫抑制。即使在没有病原体的情况下,CF患者的气道中SPMs的产生也会减少。气道中SPMs的水平与CF患者的肺功能相关。CF的预后有了很大改善,但仍然迫切需要更有效的治疗方法,以防止所有CF患者出现过度炎症、肺损伤和肺功能下降。本综述旨在强调对CF气道炎症的最新认识以及SPMs对CF气道中改变的功能可能产生的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5291/7493015/7903530c42ad/fphar-11-01290-g001.jpg

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