ArticleJCI insight2018
Chronic β2AR stimulation limits CFTR activation in human airway epithelia.
Article in JCI insight, 2018. 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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Who cites it
13 citing papers in PubMed.
- Therapeutic potential of synergistic mucociliary clearance for cystic fibrosis airways by β-adrenergic plus cholinergic agonists.The Journal of clinical investigation · 2026Article
- PM2.5 toxin benzo[a]pyrene induces life-limiting inflammation and oxidative stress in the airway by up-regulation of TRPC6 and inactivation of β2AR/CFTR signaling.bioRxiv : the preprint server for biology · 2026Article
- TGF-β induces excessive pulmonary IL-6 secretion in cystic fibrosis via PI3K.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Update on the Role of β2AR and TRPV1 in Respiratory Diseases.International journal of molecular sciences · 2024Review
- Heterogeneity in Neutrophil Extracellular Traps from Healthy Human Subjects.International journal of molecular sciences · 2023Article
- Heterogeneity in Neutrophil Extracellular Traps from Healthy Human Subjects.bioRxiv : the preprint server for biology · 2023Article
- It Takes Two to Tango! Protein-Protein Interactions behind cAMP-Mediated CFTR Regulation.International journal of molecular sciences · 2023Review
- Phenotypic Alteration of an Established Human Airway Cell Line by Media Selection.International journal of molecular sciences · 2023Article
- Receptor-mediated activation of CFTR via prostaglandin signaling pathways in the airway.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Alpha-1 antitrypsin limits neutrophil extracellular trap disruption of airway epithelial barrier function.Frontiers in immunology · 2022Article
- The Protective Effects of IL-31RA Deficiency During Bleomycin-Induced Pulmonary Fibrosis.Frontiers in immunology · 2021Article
- Case report: Three adult brothers with cystic fibrosis (delF508-delF508) maintain unusually preserved clinical profile in the absence of standard CF care.Respiratory medicine case reports · 2021Article
- Neutrophil extracellular traps activate IL-8 and IL-1 expression in human bronchial epithelia.American journal of physiology. Lung cellular and molecular physiology · 2020Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Traditional pulmonary therapies for cystic fibrosis (CF) target the downstream effects of CF transmembrane conductance regulator (CFTR) dysfunction (the cause of CF). Use of one such therapy, β-adrenergic bronchodilators (such as albuterol), is nearly universal for airway clearance. Conversely, novel modulator therapies restore function to select mutant CFTR proteins, offering a disease-modifying treatment. Recent trials of modulators targeting F508del-CFTR, the most common CFTR mutation, suggest that chronic β-agonist use may undermine clinical modulator benefits. We therefore sought to understand the impact of chronic or excess β-agonist exposure on CFTR activation in human airway epithelium. The present studies demonstrate a greater than 60% reduction in both wild-type and modulator-corrected F508del-CFTR activation following chronic exposure to short- and long-acting β-agonists. This reduction was due to reduced cellular generation of cAMP downstream of the β-2 adrenergic receptor-G protein complex. Our results point towards a posttranscriptional reduction in adenylyl cyclase function as the mechanism of impaired CFTR activation produced by prolonged β-agonist exposure. β-Agonist-induced CFTR dysfunction was sufficient to abrogate VX809/VX770 modulation of F508del-CFTR in vitro. Understanding the clinical relevance of our observations is critical for CF patients using these drugs, and for investigators to inform future CFTR modulator drug trials.
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