Chronic obstructive pulmonary disease and the modulation of CFTR by acute exposure to cigarette smoke

Hanrahan, John W.; Abu‐Arish, Asmahan; Wong, Francis; Turner, Mark J.; Carlile, Graeme W.; Thomas, David Y.; Cantin, André M.

doi:10.1152/ajpcell.00356.2022

Cited by 3 publications

(1 citation statement)

References 256 publications

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“…Ion and water movement have been extensively studied in the airways of combustible tobacco smokers. For example, both acute and chronic smoking reduce CFTR-mediated Cl − secretion and slow mucus transport in humans [31,32]. Similarly, in vitro combustible tobacco exposures decreased CFTR activity and induced ASL dehydration [32,33].…”

Section: Discussionmentioning

confidence: 99%

Vaping-Induced Proteolysis Causes Airway Surface Dehydration

Ghosh,

Coakley,

Alexis

et al. 2023

IJMS

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Proteases such as neutrophil elastase cleave and activate the epithelial sodium channel (ENaC), causing airway dehydration. Our current study explores the impact of increased protease levels in vapers’ airways on ENaC activity and airway dehydration. Human bronchial epithelial cultures (HBECs) were exposed to bronchoalveolar lavage fluid (BALF) from non-smokers, smokers and vapers. Airway surface liquid (ASL) height was measured by confocal microscopy as a marker of hydration. ENaC cleavage was measured by Western blotting. Human peripheral blood neutrophils were treated with a menthol-flavored e-liquid (Juul), and the resulting secretions were added to HBECs. BALF from smokers and vapers significantly and equally increased ENaC activity and decreased ASL height. The ASL height decrease was attenuated by protease inhibitors. Non-smokers’ BALF had no effect on ENaC or ASL height. BALF from smokers and vapers, but not non-smokers, induced ENaC cleavage. E-liquid-treated neutrophil secretions cleaved ENaC and decreased ASL height. Our study demonstrated that elevated protease levels in vapers’ airways have functional significance since they can activate ENaC, resulting in airway dehydration. Lung dehydration contributes to diseases like cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and asthma. Thus, our data predict that vaping, like smoking, will cause airway surface dehydration that likely leads to lung disease.

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Section: Discussionmentioning

confidence: 99%

Vaping-Induced Proteolysis Causes Airway Surface Dehydration

Ghosh,

Coakley,

Alexis

et al. 2023

IJMS

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Unravelling the signaling power of pollutants

Manzano-Covarrubias,

Yan,

Luu

et al. 2023

Trends in Pharmacological Sciences

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The COPD-Associated Polymorphism Impairs the CFTR Function to Suppress Excessive IL-8 Production upon Environmental Pathogen Exposure

Hinata

Fukuda

Okiyoneda

2023

IJMS

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COPD is a lifestyle-related disease resulting from irreversible damage to respiratory tissues mostly due to chronic exposure to environmental pollutants, including cigarette smoke. Environmental pathogens and pollutants induce the acquired dysfunction of the CFTR Cl- channel, which is invoked in COPD. Despite the increased incidence of CFTR polymorphism R75Q or M470V in COPD patients, the mechanism of how the CFTR variant affects COPD pathogenesis remains unclear. Here, we investigated the impact of CFTR polymorphisms (R75Q, M470V) on the CFTR function in airway epithelial cell models. While wild-type (WT) CFTR suppressed the proinflammatory cytokine production induced by COPD-related pathogens including pyocyanin (PYO), R75Q- or M470V-CFTR failed. Mechanistically, the R75Q- or M470V-CFTR fractional PM activity (FPMA) was significantly lower than WT-CFTR in the presence of PYO. Notably, the CF drug Trikafta corrected the PM expression of R75Q- or M470V-CFTR even upon PYO exposure and consequently suppressed the excessive IL-8 production. These results suggest that R75Q or M470V polymorphism impairs the CFTR function to suppress the excessive proinflammatory response to environmental pathogens associated with COPD. Moreover, Trikafta may be useful to prevent the COPD pathogenesis associated with acquired CFTR dysfunction.

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Chronic obstructive pulmonary disease and the modulation of CFTR by acute exposure to cigarette smoke

Cited by 3 publications

References 256 publications

Vaping-Induced Proteolysis Causes Airway Surface Dehydration

Vaping-Induced Proteolysis Causes Airway Surface Dehydration

Unravelling the signaling power of pollutants

The COPD-Associated Polymorphism Impairs the CFTR Function to Suppress Excessive IL-8 Production upon Environmental Pathogen Exposure

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