Turnover of the cystic fibrosis transmembrane conductance regulator (CFTR): Slow degradation of wild-type and ΔF508 CFTR in surface membrane preparations of immortalized airway epithelial cells

1996 ◽  
Vol 168 (2) ◽  
pp. 373-384 ◽  
Author(s):  
Xiaofang Wei ◽  
Robin Eisman ◽  
Jin Xu ◽  
Alan D. Harsch ◽  
Andrew E. Mulberg ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Surface Membrane ◽  
Airway Epithelial Cells ◽  
Transmembrane Conductance Regulator ◽  
Airway Epithelial ◽  
Wild Type ◽  
Transmembrane Conductance ◽  
Δf508 Cftr ◽  
Cystic Fibrosis Transmembrane

scholarly journals Deleterious impact of Pseudomonas aeruginosa on cystic fibrosis transmembrane conductance regulator function and rescue in airway epithelial cells

2015 ◽  
Vol 45 (6) ◽  
pp. 1590-1602 ◽  
Author(s):  
Nguyen Thu Ngan Trinh ◽  
Claudia Bilodeau ◽  
Émilie Maillé ◽  
Manon Ruffin ◽  
Marie-Claude Quintal ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Epithelial Cells ◽  
Short Circuit ◽  
Airway Epithelial Cells ◽  
Transmembrane Conductance Regulator ◽  
Airway Epithelial ◽  
Transmembrane Conductance ◽  
Δf508 Cftr ◽  
Cystic Fibrosis Transmembrane

The epithelial response to bacterial airway infection, a common feature of lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis, has been extensively studied. However, its impact on cystic fibrosis transmembrane conductance regulator (CFTR) channel function is not clearly defined. Our aims were, therefore, to evaluate the effect of Pseudomonas aeruginosa on CFTR function and expression in non-cystic fibrosis airway epithelial cells, and to investigate its impact on ΔF508-CFTR rescue by the VRT-325 corrector in cystic fibrosis cells.CFTR expression/maturation was evaluated by immunoblotting and its function by short-circuit current measurements.A 24-h exposure to P. aeruginosa diffusible material (PsaDM) reduced CFTR currents as well as total and membrane protein expression of the wildtype (wt) CFTR protein in CFBE-wt cells. In CFBE-ΔF508 cells, PsaDM severely reduced CFTR maturation and current rescue induced by VRT-325. We also confirmed a deleterious impact of PsaDM on wt-CFTR currents in non-cystic fibrosis primary airway cells as well as on the rescue of ΔF508-CFTR function induced by VRT-325 in primary cystic fibrosis cells.These findings show that CFTR function could be impaired in non-cystic fibrosis patients infected by P. aeruginosa. Our data also suggest that CFTR corrector efficiency may be affected by infectious components, which should be taken into account in screening assays of correctors.

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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