ArticleThe Journal of allergy and clinical immunology2010
Phosphodiesterase 4B is essential for T(H)2-cell function and development of airway hyperresponsiveness in allergic asthma.
Article in The Journal of allergy and clinical immunology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 94 citations in OpenAlex.
- The effect of the novel phosphodiesterase-4 inhibitor MEM 1414 on the allergen induced responses in mild asthma.BMC pulmonary medicine · 2014Trial
- Hierarchical classification of immune cell transcriptomes at population-scale.bioRxiv : the preprint server for biology · 2026Article
- Phosphodiesterase signaling in asthma: mechanistic insights and emerging therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- The cAMP-phosphodiesterase PDE4B2 controls peroxisome proliferator-activated receptor γ expression and the initiation of adipogenesis in 3T3-L1 cells.American journal of physiology. Endocrinology and metabolism · 2025Article
- The Mechanisms of Immunoglobulin E Sensitizations in Atopic Dermatitis.Immunology and allergy clinics of North America · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Article
- Rutaecarpine alleviates hepatic ischemia‒reperfusion injury in liver transplantation by inhibiting inflammatory response and oxidative stress.Frontiers in pharmacology · 2025Article
- Potential of phosphodiesterase 4B inhibitors in the treatment of interstitial lung disease associated with autoimmune diseases.Clinical and experimental rheumatology · 2025Review
- Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans.Cell research · 2024Article
- Menisoxoisoaporphine A, a novel oxoisoaporphine alkaloid from Menispermi Rhizoma, inhibits inflammation by targeting PDE4B.Frontiers in pharmacology · 2024Article
- Dysregulated Cyclic Nucleotide Metabolism in Alcohol-Associated Steatohepatitis: Implications for Novel Targeted Therapies.Biology · 2023Article
- Modulation of Human Dendritic Cell Functions by Phosphodiesterase-4 Inhibitors: Potential Relevance for the Treatment of Respiratory Diseases.Pharmaceutics · 2023Review
- Phosphodiesterase 4B inhibition: a potential novel strategy for treating pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Novel Anti-Inflammatory Approaches to COPD.International journal of chronic obstructive pulmonary disease · 2023Review
- Transcriptional changes in dendritic cells underlying allergen specific induced tolerance in a mouse model.Scientific reports · 2022Article
- Clinical Implication of Phosphodiesterase-4-Inhibition.International journal of molecular sciences · 2022Review
- PDE4B Is a Homeostatic Regulator of Cyclic AMP in Dendritic Cells.Frontiers in pharmacology · 2022Article
- Ligustrazine Inhibits Lung Phosphodiesterase Activity in a Rat Model of Allergic Asthma.Computational and mathematical methods in medicine · 2022Article
- The effects of BRL-50481 on ovalbumin-induced asthmatic lung inflammation exacerbated by co-exposure to Asian sand dust in the murine model.Archives of pharmacal research · 2022Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundCyclic AMP (cAMP) signaling modulates functions of inflammatory cells involved in the pathogenesis of asthma, and type 4 cAMP-specific phosphodiesterases (PDE4s) are essential components of this pathway. Induction of the PDE4 isoform PDE4B is necessary for Toll-like receptor signaling in monocytes and macrophages and is associated with T cell receptor/CD3 in T cells; however, its exact physiological function in the development of allergic asthma remains undefined.
objectivesWe investigated the role of PDE4B in the development of allergen-induced airway hyperresponsiveness (AHR) and T(H)2-driven inflammatory responses.
methodsWild-type and PDE4B(-/-) mice were sensitized and challenged with ovalbumin and AHR measured in response to inhaled methacholine. Airway inflammation was characterized by analyzing leukocyte infiltration and cytokine accumulation in the airways. Ovalbumin-stimulated cell proliferation and T(H)2 cytokine production were determined in cultured bronchial lymph node cells.
resultsMice deficient in PDE4B do not develop AHR. This protective effect was associated with a significant decrease in eosinophils recruitment to the lungs and decreased T(H)2 cytokine levels in the bronchoalveolar lavage fluid. Defects in T-cell replication, T(H)2 cytokine production, and dendritic cell migration were evident in cells from the airway-draining lymph nodes. Conversely, accumulation of the T(H)1 cytokine IFN-γ was not affected in PDE4B(-/-) mice. Ablation of the orthologous PDE4 gene PDE4A has no impact on airway inflammation.
conclusionBy relieving a cAMP-negative constraint, PDE4B plays an essential role in T(H)2-cell activation and dendritic cell recruitment during airway inflammation. These findings provide proof of concept that PDE4 inhibitors with PDE4B selectivity may have efficacy in asthma treatment.
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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.