ArticleInternational forum of allergy & rhinology2016
Cystic fibrosis transmembrane conductance regulator activation by the solvent ethanol: implications for topical drug delivery.
Article in International forum of allergy & rhinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 17 citations in OpenAlex.
- Lipopolysaccharide Causes Acquired CFTR Dysfunction in Murine Nasal Airways.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2025Article
- Azithromycin and ciprofloxacin inhibit interleukin-8 secretion without disrupting human sinonasal epithelial integrity in vitro.International forum of allergy & rhinology · 2021Article
- Korean Red Ginseng aqueous extract improves markers of mucociliary clearance by stimulating chloride secretion.Journal of ginseng research · 2021Article
- Antibiotic eluting sinus stents.Laryngoscope investigative otolaryngology · 2020Review
- Loss of cAMP-dependent stimulation of isolated cilia motility by alcohol exposure is oxidant-dependent.Alcohol (Fayetteville, N.Y.) · 2019Article
- Redox regulation of motile cilia in airway disease.Redox biology · 2019Review
- Ivacaftor improves rhinologic, psychologic, and sleep-related quality of life in G551D cystic fibrosis patients.International forum of allergy & rhinology · 2019Article
- l-Methionine anti-biofilm activity against Pseudomonas aeruginosa is enhanced by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor.International forum of allergy & rhinology · 2018Article
- Preclinical therapeutic efficacy of the ciprofloxacin-eluting sinus stent for Pseudomonas aeruginosa sinusitis.International forum of allergy & rhinology · 2018Article
- Characterization of primary rat nasal epithelial cultures in CFTR knockout rats as a model for CF sinus disease.The Laryngoscope · 2017Article
- Assessment of acquired mucociliary clearance defects using micro-optical coherence tomography.International forum of allergy & rhinology · 2017Article
- Medical and Surgical Advancements in the Management of Cystic Fibrosis Chronic Rhinosinusitis.Current otorhinolaryngology reports · 2017Article
- Sinus Microanatomy and Microbiota in a Rabbit Model of Rhinosinusitis.Frontiers in cellular and infection microbiology · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDecreased cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride (Cl) secretion across mucosal surfaces contributes to the development of airway disease by depleting airway surface liquid, increasing mucus viscosity and adhesion, and consequently hindering mucociliary clearance. We serendipitously discovered during testing of drugs solubilized in low concentrations ethanol (0.25%, 43 mM) that the control vehicle produced robust activation of CFTR-mediated Cl(-) transport. The objective of the current study is to investigate low concentrations of ethanol for effects on Cl(-) secretion and ciliary beat frequency (CBF).
methodsWild-type (WT) and transgenic CFTR(-/-) primary murine nasoseptal epithelial (MNSE) cultures and WT and F508del/F508del human sinonasal epithelial (HSNE) cultures were subjected to transepithelial ion transport measurements using pharmacologic manipulation in Ussing chambers. CBF activation was also monitored. Murine nasal potential difference (NPD) was measured in vivo.
resultsUssing chamber tracings revealed ethanol activated CFTR-mediated Cl transport in a dose-dependent fashion in WT MNSE (n = 4, p < 0.05) and HSNE (n = 4, p < 0.05). Ethanol also significantly increased CBF (fold change) in WT MNSE cultures in a dose-dependent fashion (phosphate-buffered saline [PBS], 1.33 ± 0.04; 0.25% ethanol, 1.37 ± 0.09; 0.5% ethanol, 1.53 ± 0.06 [p < 0.05]; 1% ethanol, 1.62 ± 0.1 [p < 0.05]). Lack of stimulation in CFTR(-/-) and F508del/F508del cultures indicated activity was dependent on the presence of intact functional CFTR. Ethanol perfusion (0.5%) resulted in a significant -3.5-mV mean NPD polarization when compared to control solution (p < 0.05).
conclusionThe observation that brief exposure of ethanol stimulated Cl(-) secretion via CFTR-mediated pathways indicates its possible use as topical aerosol delivered alone or in combination with other CFTR activators for diseases of dysfunctional mucociliary clearance (MCC) in chronic rhinosinusitis (CRS).
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