ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Anchored PDE4 regulates chloride conductance in wild-type and ΔF508-CFTR human airway epithelia.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Use of a 4-week up-titration regimen of roflumilast in patients with severe COPD.International journal of chronic obstructive pulmonary disease · 2018Trial
- Beyond the mutations: spatiotemporal regulation of CFTR by cAMP and calcium signaling in epithelial physiology and cystic fibrosis.Cellular & molecular biology letters · 2025Review
- A novel drug series optimized to address cystic fibrosis and other CFTR deficiency diseases of human airways.npj drug discovery · 2025Article
- PDE4-Selective Inhibition in Chronic Obstructive Pulmonary Disease and Pulmonary Fibrosis: Different Agents or Different Targets?Life (Basel, Switzerland) · 2025Review
- Article
- Cell type-specific regulation of CFTR trafficking-on the verge of progress.Frontiers in cell and developmental biology · 2024Review
- Therapeutic Targets and Precision Medicine in COPD: Inflammation, Ion Channels, Both, or Neither?International journal of molecular sciences · 2023Review
- Agonists and hydrogen peroxide mediate hyperoxidation of β2-adrenergic receptor in airway epithelial cells: Implications for tachyphylaxis to β2-agonists in constrictive airway disorders.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- It Takes Two to Tango! Protein-Protein Interactions behind cAMP-Mediated CFTR Regulation.International journal of molecular sciences · 2023Review
- Review
- A PI3Kγ mimetic peptide triggers CFTR gating, bronchodilation, and reduced inflammation in obstructive airway diseases.Science translational medicine · 2022Article
- The cAMP-phosphodiesterase 4 (PDE4) controls β-adrenoceptor- and CFTR-dependent saliva secretion in mice.The Biochemical journal · 2021Article
- Modulation of cAMP metabolism for CFTR potentiation in human airway epithelial cells.Scientific reports · 2021Article
- Type-4 Phosphodiesterase (PDE4) Blockade Reduces NETosis in Cystic Fibrosis.Frontiers in pharmacology · 2021Article
- Inhaled Dual Phosphodiesterase 3/4 Inhibitors for the Treatment of Patients with COPD: A Short Review.International journal of chronic obstructive pulmonary disease · 2021Review
- PAN-selective inhibition of cAMP-phosphodiesterase 4 (PDE4) induces gastroparesis in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Dominant-Negative Attenuation of cAMP-Selective Phosphodiesterase PDE4D Action Affects Learning and Behavior.International journal of molecular sciences · 2020Article
- Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors.Frontiers in pharmacology · 2020Review
- Small-molecule allosteric activators of PDE4 long form cyclic AMP phosphodiesterases.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Dexamethasone Inhibits Synergistic Induction of PDE4B Expression by Roflumilast and Bacterium NTHi.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) that impair its expression and/or chloride channel function. Here, we provide evidence that type 4 cyclic nucleotide phosphodiesterases (PDE4s) are critical regulators of the cAMP/PKA-dependent activation of CFTR in primary human bronchial epithelial cells. In non-CF cells, PDE4 inhibition increased CFTR activity under basal conditions (ΔISC 7.1 μA/cm(2)) and after isoproterenol stimulation (increased ΔISC from 13.9 to 21.0 μA/cm(2)) and slowed the return of stimulated CFTR activity to basal levels by >3-fold. In cells homozygous for ΔF508-CFTR, the most common mutation found in CF, PDE4 inhibition alone produced minimal channel activation. However, PDE4 inhibition strongly amplified the effects of CFTR correctors, drugs that increase expression and membrane localization of CFTR, and/or CFTR potentiators, drugs that increase channel gating, to reach ∼ 25% of the chloride conductance observed in non-CF cells. Biochemical studies indicate that PDE4s are anchored to CFTR and mediate a local regulation of channel function. Taken together, our results implicate PDE4 as an important determinant of CFTR activity in airway epithelia, and support the use of PDE4 inhibitors to potentiate the therapeutic benefits of CFTR correctors and potentiators.
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