ArticleAllergy2017
Protein phosphatase 5 mediates corticosteroid insensitivity in airway smooth muscle in patients with severe asthma.
Article in Allergy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Role of miR-191-3p in HDM-induced airway epithelial inflammation by targeting CD247 in allergic asthma.BMC immunology · 2026Article
- How post-translational modifications impact glucocorticoid receptor function in human pathologies.Cell communication and signaling : CCS · 2026Review
- Nrf2: A Promising Therapeutic Target for Glucocorticoid-Resistant Chronic Rhinosinusitis.Clinical and experimental otorhinolaryngology · 2026Review
- Effects ofPlants (Basel, Switzerland) · 2023Article
- Glucocorticoid Insensitivity in Asthma: The Unique Role for Airway Smooth Muscle Cells.International journal of molecular sciences · 2022Review
- Inhibition of Spleen Tyrosine Kinase Restores Glucocorticoid Sensitivity to Improve Steroid-Resistant Asthma.Frontiers in pharmacology · 2022Article
- Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD.Antioxidants (Basel, Switzerland) · 2021Review
- Insights into glucocorticoid responses derived from omics studies.Pharmacology & therapeutics · 2021Review
- Metal-Stimulated Interleukin-6 Production Through a Proton-Sensing Receptor, Ovarian Cancer G Protein-Coupled Receptor 1, in Human Bronchial Smooth Muscle Cells: A Response Inhibited by Dexamethasone.Journal of inflammation research · 2021Article
- Human Lung Mast Cells Impair Corticosteroid Responsiveness in Human Airway Smooth Muscle Cells.Frontiers in allergy · 2021Article
- Important lessons learned from studies on the pharmacology of glucocorticoids in human airway smooth muscle cells: Too much of a good thing may be a problem.Pharmacology & therapeutics · 2020Review
- Expression of corticosteroid-regulated genes by PBMCs in children with asthma.The Journal of allergy and clinical immunology · 2019Article
- The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma.Frontiers in pharmacology · 2019Review
- Highlights and recent developments in airway diseases in EAACI journals (2017).Clinical and translational allergy · 2018Review
- Reslizumab and Eosinophilic Asthma: One Step Closer to Precision Medicine?Frontiers in immunology · 2017Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe mechanisms driving glucocorticoid (GC) insensitivity in patients with severe asthma are still unknown. Recent evidence suggests the existence of GC-insensitive pathways in airway smooth muscle (ASM) caused by a defect in GC receptor (GRα) function. We examined whether other mechanisms could potentially explain the reduced sensitivity of ASM cells to GC in severe asthmatics.
methodsAirway smooth muscle cells from healthy and severe asthmatic subjects were treated with TNF-α and responses to corticosteroids in both cohorts were compared by ELISA, immunoblot, immunohistochemistry and real-time PCR. Immunohistochemistry and flow cytometry assays were used to assess the expression of the protein phosphatase PP5 in endobronchial biopsies and ASM cells.
resultsThe production of CCL11 and CCL5 by TNF-α was insensitive to both fluticasone and dexamethasone in ASM cells from severe asthmatic compared to that in healthy subjects. Fluticasone-induced GRα nuclear translocation, phosphorylation at serine 211 and expression of GC-induced leucine zipper (GILZ) were significantly reduced in ASM cells from severe asthmatics compared to responses in healthy subjects. Levels of PP5 were increased in ASM cells from severe asthmatics and PP5 knockdown using siRNA restored fluticasone repressive action on chemokine production and its ability to induce GRα nuclear translocation and GRE-dependent GILZ expression. In vivo PP5 expression was also increased in the ASM bundles in endobronchial biopsies in severe asthmatics.
conclusionsPP5-dependent impairment of GRα function represents a novel mechanism driving GC insensitivity in ASM in severe asthma.
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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.