Glutathione permeability of CFTR

1998 ◽  
Vol 275 (1) ◽  
pp. C323-C326 ◽  
Author(s):  
Paul Linsdell ◽  
John W. Hanrahan
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Ion Channel ◽  
Airway Epithelial Cells ◽  
Transmembrane Conductance Regulator ◽  
Airway Epithelial ◽  
Transmembrane Conductance ◽  
High Concentrations ◽  
Cystic Fibrosis Transmembrane ◽  
Glutathione Transport

The cystic fibrosis transmembrane conductance regulator (CFTR) forms an ion channel that is permeable both to Cl− and to larger organic anions. Here we show, using macroscopic current recording from excised membrane patches, that the anionic antioxidant tripeptide glutathione is permeant in the CFTR channel. This permeability may account for the high concentrations of glutathione that have been measured in the surface fluid that coats airway epithelial cells. Furthermore, loss of this pathway for glutathione transport may contribute to the reduced levels of glutathione observed in airway surface fluid of cystic fibrosis patients, which has been suggested to contribute to the oxidative stress observed in the lung in cystic fibrosis. We suggest that release of glutathione into airway surface fluid may be a novel function of CFTR.

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.

scholarly journals ACE2 expression and localization are regulated by CFTR: implications beyond cystic fibrosis

2021 ◽  
Author(s):  
Valentino Bezzerri ◽  
Valentina Gentili ◽  
Martina Api ◽  
Alessia Finotti ◽  
Chiara Papi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Host Factors ◽  
Transmembrane Conductance Regulator ◽  
Airway Epithelial ◽  
Transmembrane Conductance ◽  
Angiotensin Converting Enzyme 2 ◽  
Cystic Fibrosis Transmembrane ◽  
Severe Pulmonary Disease

As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis (CF) could be considered a comorbidity for coronavirus disease 2019 (COVID-19)1. Instead, CF seems to constitute an advantage in COVID-19 infection2-5. To clarify whether host factors expressed by the CF epithelia may influence COVID-19 progression, we investigated the expression of SARS-CoV-2 receptor and coreceptors in primary airway epithelial cells. We found that angiotensin converting enzyme 2 (ACE2) expression and localization are regulated by cystic fibrosis transmembrane conductance regulator (CFTR) channels. Consistently, our results indicate that dysfunctional CFTR channels alter susceptibility to SARS-CoV-2 infection, resulting in reduced viral infection in CF cells. Depending on the pattern of ACE2 expression, the SARS-CoV-2 spike (S) protein induced high levels of Interleukin (IL)-6 in healthy donor-derived primary airway epithelial cells but a very weak response in primary CF cells. Collectively, these data support the hypothesis that CF condition is unfavorable for SARS-CoV-2 infection.

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