ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Cytokine-Induced Glucocorticoid Resistance from Eosinophil Activation: Protein Phosphatase 5 Modulation of Glucocorticoid Receptor Phosphorylation and Signaling.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Mechanisms of glucocorticoid resistance in hypereosinophilic syndromes.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2019Trial
- Clinical diagnosis and treatment of eosinophilic asthma by respiratory physicians in China: a cross-sectional survey.Journal of thoracic disease · 2026Article
- Impact of eosinophil levels on postoperative clinical outcomes in patients undergoing extracorporeal circulation: a retrospective cohort study.BMC cardiovascular disorders · 2026Article
- Glucocorticoid receptor dynamics and neuroinflammation in chronic restraint stress-induced mechanical allodynia in female rats.The journal of pain · 2025Article
- IL-8 promotes pyroptosis through ERK pathway and mediates glucocorticoid resistance in chronic rhinosinusitis with nasal polyps.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- PBMC-engrafted humanized mice models for evaluating immune-related and anticancer drug delivery systems.Frontiers in molecular biosciences · 2024Review
- Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.Physiological reviews · 2024Review
- Inadequate therapeutic responses to glucocorticoid treatment in bronchial asthma.The Journal of international medical research · 2023Review
- Impacts of eosinophil percentage on prognosis acute type A aortic dissection patients.BMC cardiovascular disorders · 2022Article
- Eosinophil-to-Monocyte Ratio is a Potential Predictor of Prognosis in Acute Ischemic Stroke Patients After Intravenous Thrombolysis.Clinical interventions in aging · 2021Article
- Potential Role of Mast Cells in Regulating Corticosteroid Insensitivity in Severe Asthma.Advances in experimental medicine and biology · 2021Article
- Pleiotropic Effects of Glucocorticoids on the Immune System in Circadian Rhythm and Stress.Frontiers in immunology · 2021Review
- Apoptosis of Eosinophil Granulocytes.Biology · 2020Review
- Protein phosphatase 1 alpha enhances glucocorticoid receptor activity by a mechanism involving phosphorylation of serine-211.Molecular and cellular endocrinology · 2020Article
- [Liver failure and glucocorticoid resistance].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2020Article
- Immunopathology and biology-based treatment of steroid-refractory graft-versus-host disease.Blood · 2020Review
- Structure and function of the co-chaperone protein phosphatase 5 in cancer.Cell stress & chaperones · 2020Review
- Nuclear Receptors in Asthma: Empowering Classical Molecules Against a Contemporary Ailment.Frontiers in immunology · 2020Review
- Eosinopenia is a predictive factor for the severity of acute ischemic stroke.Neural regeneration research · 2019Article
- The Management of Glucocorticoid Therapy in Liver Failure.Frontiers in immunology · 2019Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The mechanisms contributing to persistent eosinophil activation and poor eosinopenic response to glucocorticoids in severe asthma are poorly defined. We examined the effect of cytokines typically overexpressed in the asthmatic airways on glucocorticoid signaling in in vitro activated eosinophils. An annexin V assay used to measure eosinophil apoptosis showed that cytokine combinations of IL-2 plus IL-4 as well as TNF-α plus IFN-γ, or IL-3, GM-CSF, and IL-5 alone significantly diminished the proapoptotic response to dexamethasone. We found that IL-2 plus IL-4 resulted in impaired phosphorylation and function of the nuclear glucocorticoid receptor (GCR). Proteomic analysis of steroid sensitive and resistant eosinophils identified several differentially expressed proteins, namely protein phosphatase 5 (PP5), formyl peptide receptor 2, and annexin 1. Furthermore, increased phosphatase activity of PP5 correlated with impaired phosphorylation of the GCR. Importantly, suppression of PP5 expression with small interfering RNA restored proper phosphorylation and the proapoptotic function of the GCR. We also examined the effect of lipoxin A4 on PP5 activation by IL-2 plus IL-4. Similar to PP5 small interfering RNA inhibition, pretreatment of eosinophils with lipoxin A4 restored GCR phosphorylation and the proaptoptotic function of GCs. Taken together, our results showed 1) a critical role for PP5 in cytokine-induced resistance to GC-mediated eosinophil death, 2) supported the dependence of GCR phosphorylation on PP5 activity, and 3) revealed that PP5 is a target of the lipoxin A4-induced pathway countering cytokine-induced resistance to GCs in eosinophils.
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