ArticleThe Journal of clinical investigation2021
Inflammatory cytokines TNF-α and IL-17 enhance the efficacy of cystic fibrosis transmembrane conductance regulator modulators.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Impact of Gene Modifiers on Cystic Fibrosis Phenotypic Profiles: A Systematic Review.Human mutation · 2024Pooled it
- Genetic and chemical correction of cystic fibrosis reduces airway susceptibility to SARS-CoV-2.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- The cystic fibrosis airway cytokine interleukin-1β enhances cystic fibrosis transmembrane conductance regulator modulator efficacy.ERJ open research · 2026Article
- PDE4 Inhibitor Apremilast Rebalances Inflammatory Responses to Pseudomonas aeruginosa Infection in CF Rats.bioRxiv : the preprint server for biology · 2026Article
- Effects of cAMP and CFTR modulation on apical fluid pH in human airway Calu-3 cells.Physiological reports · 2026Article
- Transcriptomic and functional responses of the cystic fibrosis airway epithelium to CFTR modulator therapy.JCI insight · 2025Article
- Pseudomonas infections persisting after CFTR modulators are widespread throughout the lungs and drive lung inflammation.Cell host & microbe · 2025Article
- Deleterious effect ofERJ open research · 2025Article
- From CFTR to a CF signalling network: a systems biology approach to study Cystic Fibrosis.BMC genomics · 2024Article
- Allergic Bronchopulmonary Aspergillosis (ABPA) in the Era of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators.Journal of fungi (Basel, Switzerland) · 2024Review
- Predictors of Sinonasal Improvement After Highly Effective Modulator Therapy in Adults with Cystic Fibrosis.The Laryngoscope · 2024Observational
- Cystic fibrosis.Nature reviews. Disease primers · 2024Review
- Article
- Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells.Respiratory research · 2024Article
- Epithelial responses to CFTR modulators are improved by inflammatory cytokines and impaired by antiinflammatory drugs.JCI insight · 2024Article
- Dynamic measurement of airway surface liquid volume with anLab on a chip · 2024Article
- Representation and quantification of module activity from omics data with rROMA.NPJ systems biology and applications · 2024Article
- Multiple Regulatory Signals and Components in the Modulation of Bicarbonate Transporters.Pharmaceutics · 2024Review
- Cystic fibrosis airway inflammation enables elexacaftor/tezacaftor/ivacaftor-mediated rescue of N1303KERJ open research · 2024Article
- Two rare variants that affect the same amino acid in CFTR have distinct responses to ivacaftor.The Journal of physiology · 2024Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Without cystic fibrosis transmembrane conductance regulator-mediated (CFTR-mediated) HCO3- secretion, airway epithelia of newborns with cystic fibrosis (CF) produce an abnormally acidic airway surface liquid (ASL), and the decreased pH impairs respiratory host defenses. However, within a few months of birth, ASL pH increases to match that in non-CF airways. Although the physiological basis for the increase is unknown, this time course matches the development of inflammation in CF airways. To learn whether inflammation alters CF ASL pH, we treated CF epithelia with TNF-α and IL-17 (TNF-α+IL-17), 2 inflammatory cytokines that are elevated in CF airways. TNF-α+IL-17 markedly increased ASL pH by upregulating pendrin, an apical Cl-/HCO3- exchanger. Moreover, when CF epithelia were exposed to TNF-α+IL-17, clinically approved CFTR modulators further alkalinized ASL pH. As predicted by these results, in vivo data revealed a positive correlation between airway inflammation and CFTR modulator-induced improvement in lung function. These findings suggest that inflammation is a key regulator of HCO3- secretion in CF airways. Thus, they explain earlier observations that ASL pH increases after birth and indicate that, for similar levels of inflammation, the pH of CF ASL is abnormally acidic. These results also suggest that a non-cell-autonomous mechanism, airway inflammation, is an important determinant of the response to CFTR modulators.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.