ArticleJCI insight2018
A pathophysiological role of PDE3 in allergic airway inflammation.
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 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Treatment of chronic obstructive pulmonary disease: current pipeline and new opportunities.Nature reviews. Drug discovery · 2026Review
- Chronic Obstructive Pulmonary Disease (COPD): Developments in Pharmacological Treatments.Drugs · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Advancing Obstructive Airway Disease Treatment: Dual PDE3/4 Inhibition as a Therapeutic Strategy.Cells · 2025Review
- Phosphodiesterase Inhibition as a Therapeutic Strategy for Chronic Obstructive Pulmonary Disease: Where We Have Been and What Lies Ahead.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2025Article
- Neutrophil Extracellular Traps as a Biomarker in Refractory Non-Type 2 CRSwNP.Allergy, asthma & immunology research · 2024Article
- Perspectives of PDE inhibitor on treating idiopathic pulmonary fibrosis.Frontiers in pharmacology · 2023Review
- Salicylate Sodium Suppresses Monocyte Chemoattractant Protein-1 Production by Directly Inhibiting Phosphodiesterase 3B in TNF-α-Stimulated Adipocytes.International journal of molecular sciences · 2022Article
- Therapeutic Approaches for Chronic Obstructive Pulmonary Disease (COPD) Exacerbations.Pathogens (Basel, Switzerland) · 2022Review
- Oral enoximone allows the reduction and discontinuation of inhaled steroids and beta2 agonists in asthmatic children.International journal of pediatrics & adolescent medicine · 2022Article
- Inhaled Phosphodiesterase Inhibitors for the Treatment of Chronic Obstructive Pulmonary Disease.Drugs · 2021Review
- MiR-139-5p has an antidepressant-like effect by targeting phosphodiesterase 4D to activate the cAMP/PKA/CREB signaling pathway.Annals of translational medicine · 2021Article
- Impacts of anti-inflammatory phosphodiesterase inhibitors on a murine model of chronic pulmonary inflammation.Pharmacology research & perspectives · 2021Article
- PDE3-inhibitor enoximone prevented mechanical ventilation in patients with SARS-CoV-2 pneumonia.Experimental lung research · 2021Article
- Phosphodiesterase Inhibitors in Acute Lung Injury: What Are the Perspectives?International journal of molecular sciences · 2021Review
- Evaluation of Real-Life Investigational Use of Enoximone in Asthma, the Third Step in Drug Repurposing: A Preliminary Report.Canadian respiratory journal · 2021Article
- New Avenues for Phosphodiesterase Inhibitors in Asthma.Journal of experimental pharmacology · 2021Review
- Phosphodiesterase-4 Inhibitors for Non-COPD Respiratory Diseases.Frontiers in pharmacology · 2021Review
- (Oral) enoximone in asthma.ERJ open research · 2020Article
- Phosphodiesterase isoforms and cAMP compartments in the development of new therapies for obstructive pulmonary diseases.Current opinion in pharmacology · 2020Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphodiesterase 3 (PDE3) and PDE4 regulate levels of cyclic AMP, which are critical in various cell types involved in allergic airway inflammation. Although PDE4 inhibition attenuates allergic airway inflammation, reported side effects preclude its application as an antiasthma drug in humans. Case reports showed that enoximone, which is a smooth muscle relaxant that inhibits PDE3, is beneficial and lifesaving in status asthmaticus and is well tolerated. However, clinical observations also showed antiinflammatory effects of PDE3 inhibition. In this study, we investigated the role of PDE3 in a house dust mite-driven (HDM-driven) allergic airway inflammation (AAI) model that is characterized by T helper 2 cell activation, eosinophilia, and reduced mucosal barrier function. Compared with wild-type (WT) littermates, mice with a targeted deletion of the PDE3A or PDE3B gene showed significantly reduced HDM-driven AAI. Therapeutic intervention in WT mice showed that all hallmarks of HDM-driven AAI were abrogated by the PDE3 inhibitors enoximone and milrinone. Importantly, we found that enoximone also reduced the upregulation of the CD11b integrin on mouse and human eosinophils in vitro, which is crucial for their recruitment during allergic inflammation. This study provides evidence for a hitherto unknown antiinflammatory role of PDE3 inhibition in allergic airway inflammation and offers a potentially novel treatment approach.
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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.