ArticleBritish journal of pharmacology2018
Cigarette smoke up-regulates PDE3 and PDE4 to decrease cAMP in airway cells.
Article in British journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Inhibition of EPAC1 Prevents Neuronal Death Mediated by Diesel Exhaust Particles in Ferroptotic Cell Death Conditions.Antioxidants (Basel, Switzerland) · 2026Article
- Respiratory Ciliary Beat Frequency in COPD: Balancing Oxidative Stress and Pharmacological Treatment.Antioxidants (Basel, Switzerland) · 2025Review
- Comparative metabolomic analysis of human lung slices (hu-PCLS) exposed to either standard or FLASH protons: a pilot study.Radiation oncology (London, England) · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Advancing Obstructive Airway Disease Treatment: Dual PDE3/4 Inhibition as a Therapeutic Strategy.Cells · 2025Review
- What every clinician should know about inflammation in COPD.ERJ open research · 2024Review
- High throughput screening of airway constriction in mouse lung slices.Scientific reports · 2024Article
- Nicotine Impairs Smooth Muscle cAMP Signaling and Vascular Reactivity.Microcirculation (New York, N.Y. : 1994) · 2024Article
- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
- Real-Time cAMP Dynamics in Live Cells Using the Fluorescent cAMP Difference Detector In Situ.Journal of visualized experiments : JoVE · 2024Article
- 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
- Single cell RNA-sequencing of human precision-cut lung slices: A novel approach to study the effect of vaping and viral infection on lung health.Innate immunity · 2023Article
- A transcriptomics-guided drug target discovery strategy identifies receptor ligands for lung regeneration.Science advances · 2022Article
- Capsaicin suppresses ciliary function, while inducing permeability in bronchial epithelial cell cultures of COPD patients.Frontiers in pharmacology · 2022Article
- The Involvement of PDE4 in the Protective Effects of Melatonin on Cigarette-Smoke-Induced Chronic Obstructive Pulmonary Disease.Molecules (Basel, Switzerland) · 2021Article
- Whole-Genome Analysis of De Novo Somatic Point Mutations Reveals Novel Mutational Biomarkers in Pancreatic Cancer.Cancers · 2021Article
- Nicotinic α7 acetylcholine receptor (α7nAChR) in human airway smooth muscle.Archives of biochemistry and biophysics · 2021Article
- A Robust Protocol for Decellularized Human Lung Bioink Generation Amenable to 2D and 3D Lung Cell Culture.Cells · 2021Article
- PDE4 inhibition as a therapeutic strategy for improvement of pulmonary dysfunctions in Covid-19 and cigarette smoking.Biochemical pharmacology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposecAMP is a central second messenger that broadly regulates cell function and can underpin pathophysiology. In chronic obstructive pulmonary disease, a lung disease primarily provoked by cigarette smoke (CS), the activation of cAMP-dependent pathways, via inhibition of hydrolyzing PDEs, is a major therapeutic strategy. Mechanisms that disrupt cAMP signalling in airway cells, in particular regulation of endogenous PDEs, are poorly understood. EXPERIMENTAL APPROACH: We used a novel Förster resonance energy transfer (FRET) based cAMP biosensor in mice in vivo, ex vivo precision cut lung slices (PCLS) and in human cell models, in vitro, to track the effects of CS exposure. KEY
resultsUnder fenoterol stimulation, FRET responses to cilostamide were significantly increased in in vivo, ex vivo PCLS exposed to CS and in human airway smooth muscle cells exposed to CS extract. FRET signals to rolipram were only increased in the in vivo CS model. Under basal conditions, FRET responses to cilostamide and rolipram were significantly increased in in vivo, ex vivo PCLS exposed to CS. Elevated FRET signals to rolipram correlated with a protein up-regulation of PDE4 subtypes. In ex vivo PCLS exposed to CS extract, rolipram reversed down-regulation of ciliary beating frequency, whereas only cilostamide significantly increased airway relaxation of methacholine pre-contracted airways. CONCLUSION AND IMPLICATIONS: Exposure to CS, in vitro or in vivo, up-regulated expression and activity of both PDE3 and PDE4, which affected real-time cAMP dynamics. These mechanisms determine the availability of cAMP and can contribute to CS-induced pulmonary pathophysiology.
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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.