scholarly journals Modulation of Ion Transport to Restore Airway Hydration in Cystic Fibrosis

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 453
Author(s):  
James A. Reihill ◽  
Lisa E. J. Douglas ◽  
S. Lorraine Martin
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Genetic Disorder ◽  
Airway Epithelial Cells ◽  
Transmembrane Conductance Regulator ◽  
Airway Epithelial ◽  
Loss Of Function ◽  
Transmembrane Conductance ◽  
Infection And Inflammation ◽  
Cf Transmembrane Conductance Regulator

Cystic fibrosis (CF) is a life-limiting genetic disorder caused by loss-of-function mutations in the gene which codes for the CF transmembrane conductance regulator (CFTR) Cl− channel. Loss of Cl− secretion across the apical membrane of airway lining epithelial cells results in dehydration of the airway surface liquid (ASL) layer which impairs mucociliary clearance (MCC), and as a consequence promotes bacterial infection and inflammation of the airways. Interventions that restore airway hydration are known to improve MCC. Here we review the ion channels present at the luminal surface of airway epithelial cells that may be targeted to improve airway hydration and MCC in CF airways.

Treating the Airway Consequences of Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction

2019 ◽  
Vol 40 (06) ◽  
pp. 751-761
Author(s):  
Demet Toprak ◽  
Chelsea Davis ◽  
Margaret Rosenfeld
Keyword(s):  
Cystic Fibrosis ◽  
Airway Epithelial Cells ◽  
Transmembrane Conductance Regulator ◽  
Airway Epithelial ◽  
National Guidelines ◽  
Transmembrane Conductance ◽  
Infection And Inflammation ◽  
Surface Liquid ◽  
Cf Transmembrane Conductance Regulator ◽  
Cystic Fibrosis Transmembrane

AbstractIn cystic fibrosis (CF), absent or dysfunctional CF transmembrane conductance regulator (CFTR) on the surface of airway epithelial cells causes abnormal mucociliary clearance, leading to chronic endobronchial infection and inflammation, in turn resulting in life-shortening progressive obstructive lung disease and structural airway damage. Fortunately, CF-specific therapies have been developed that improve lung function and reduce pulmonary exacerbations, contributing significantly to improved survival over the past 4 decades. Therapies not originally developed for CF, such as bronchodilators and corticosteroids, are also widely used by people living with CF. Therapies to be reviewed in this article include mucolytics, airway surface liquid hydrators, anti-inflammatory medications, bronchodilators, inhaled and oral antibiotics, and airway clearance techniques. Determining which therapies to utilize can be challenging, as there is variable evidence for each treatment, differing national guidelines, few head-to-head studies, potential for drug–drug interactions, and synergistic toxicities, as well as issues with burden of care. In this review, we summarize the mechanism of action and available evidence, and compare national guidelines for each major medication used to treat the airway consequences of CFTR dysfunction.

scholarly journals Infection of Polarized Airway Epithelial Cells by Normal and Small-Colony Variant Strains of Staphylococcus aureus Is Increased in Cells with Abnormal Cystic Fibrosis Transmembrane Conductance Regulator Function and Is Influenced by NF-κB

2011 ◽  
Vol 79 (9) ◽  
pp. 3541-3551 ◽  
Author(s):  
Gabriel Mitchell ◽  
Gilles Grondin ◽  
Ginette Bilodeau ◽  
André M. Cantin ◽  
François Malouin
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Transmembrane Conductance Regulator ◽  
Airway Epithelial ◽  
Transmembrane Conductance ◽  
Infection Level ◽  
Content Type ◽  
Small Colony ◽  
Cystic Fibrosis Transmembrane

ABSTRACTThe infection of nonphagocytic host cells byStaphylococcus aureusand more particularly by small-colony variants (SCVs) may contribute to the persistence of this pathogen in the lungs of cystic fibrosis (CF) patients. The development of chronic infections is also thought to be facilitated by the proinflammatory status of CF airways induced by an activation of NF-κB. The aim of this study was to compare the infection of non-CF and CF-like airway epithelial cells byS. aureusstrains (normal and SCVs) and to determine the impact of the interaction between cystic fibrosis transmembrane conductance regulator (CFTR) and NF-κB on the infection level of these cells byS. aureus. We developed anS. aureusinfection model using polarized airway epithelial cells grown at the air-liquid interface and expressing short hairpin RNAs directed against CFTR to mimic the CF condition. A pair of genetically related CF coisolates with the normal and SCV phenotypes was characterized and used. Infection of both cell lines (non-CF and CF-like) was more productive with the SCV strain than with its normal counterpart. However, both normal and SCV strains infected more CF-like than non-CF cells. Accordingly, inhibition of CFTR function by CFTRinh-172 increased theS. aureusinfection level. Experimental activation of NF-κB also increased the level of infection of polarized pulmonary epithelial cells byS. aureus, an event that could be associated with that observed when CFTR function is inhibited or impaired. This study supports the hypothesis that the proinflammatory status of CF tissues facilitates the infection of pulmonary epithelial cells byS. aureus.

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