ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Enhanced Ca2+ entry due to Orai1 plasma membrane insertion increases IL-8 secretion by cystic fibrosis airways.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 69 citations in OpenAlex.
- Immune sentinel function of nasal mucosal epithelial cells in allergic rhinitis: a review on barrier damage and inflammatory amplification loops regulated by calcium signalling.Frontiers in immunology · 2026Review
- Beyond the mutations: spatiotemporal regulation of CFTR by cAMP and calcium signaling in epithelial physiology and cystic fibrosis.Cellular & molecular biology letters · 2025Review
- Neutrophil store-operated CaJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2025Article
- Culture conditions differentially regulate the inflammatory niche and cellular phenotype of tracheobronchial basal stem cells.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- EMC3 is critical for CFTR function and calcium mobilization in the mouse intestinal epithelium.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- The F508del-CFTR trafficking correctors elexacaftor and tezacaftor are CFTR-independent CaRespiratory research · 2024Article
- Culture Conditions Differentially Regulate the Inflammatory Niche and Cellular Phenotype of Tracheo-Bronchial Basal Stem Cells.bioRxiv : the preprint server for biology · 2024Article
- Calcium Signaling in Airway Epithelial Cells: Current Understanding and Implications for Inflammatory Airway Disease.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Pharmacological inhibitors of the cystic fibrosis transmembrane conductance regulator exert off-target effects on epithelial cation channels.Pflugers Archiv : European journal of physiology · 2023Article
- Super resolution microscopy analysis reveals increased Orai1 activity in asthma and cystic fibrosis lungs.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2023Article
- Impaired regulation of PMCA activity by defective CFTR expression promotes epithelial cell damage in alcoholic pancreatitis and hepatitis.Cellular and molecular life sciences : CMLS · 2022Article
- Update on Calcium Signaling in Cystic Fibrosis Lung Disease.Frontiers in pharmacology · 2021Review
- Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations.Cellular and molecular life sciences : CMLS · 2020Review
- Salivary Cytokines and Airways Disease Severity in Patients with Cystic Fibrosis.Diagnostics (Basel, Switzerland) · 2020Article
- TMEM16A: An Alternative Approach to Restoring Airway Anion Secretion in Cystic Fibrosis?International journal of molecular sciences · 2020Review
- Role of Cystic Fibrosis Bronchial Epithelium in Neutrophil Chemotaxis.Frontiers in immunology · 2020Review
- The Role of Specialized Pro-Resolving Mediators in Cystic Fibrosis Airways Disease.Frontiers in pharmacology · 2020Review
- The CCT chaperonin is a novel regulator of CaScience advances · 2018Article
- Phagocytosis depends on TRPV2-mediated calcium influx and requires TRPV2 in lipids rafts: alteration in macrophages from patients with cystic fibrosis.Scientific reports · 2018Article
- Study of the Endogenous CRAC Channel Using shRNA-Mediated Gene Silencing.Methods in molecular biology (Clifton, N.J.) · 2018Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR). The most common mutation, ΔF508, causes retention of CFTR in the endoplasmic reticulum (ER). Some CF abnormalities can be explained by altered Ca(2+) homeostasis, although it remains unknown how CFTR influences calcium signaling. This study examined the novel hypothesis that store-operated calcium entry (SOCE) through Orai1 is abnormal in CF. The significance of Orai1-mediated SOCE for increased interleukin-8 (IL-8) expression in CF was also investigated. CF and non-CF human airway epithelial cell line and primary cells (obtained at lung transplantation) were used in Ca(2+) imaging, electrophysiology, and fluorescence imaging experiments to explore differences in Orai1 function in CF vs. non-CF cells. Protein expression and localization was assessed by Western blots, cell surface biotinylation, ELISA, and image correlation spectroscopy (ICS). We show here that store-operated Ca(2+) entry (SOCE) is elevated in CF human airway epithelial cells (hAECs; ≈ 1.8- and ≈ 2.5-fold for total Ca(2+)(i) increase and Ca(2+) influx rate, respectively, and ≈ 2-fold increase in the I(CRAC) current) and is caused by increased exocytotic insertion (≈ 2-fold) of Orai1 channels into the plasma membrane, which is normalized by rescue of ΔF508-CFTR trafficking to the cell surface. Augmented SOCE in CF cells is a major factor leading to increased IL-8 secretion (≈ 2-fold). CFTR normally down-regulates the Orai1/stromal interaction molecule 1 (STIM1) complex, and loss of this inhibition due to the absence of CFTR at the plasma membrane helps to explain the potentiated inflammatory response in CF cells.
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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.