ArticleJournal of clinical immunology2013
Glucocorticoid receptor-beta up-regulation and steroid resistance induction by IL-17 and IL-23 cytokine stimulation in peripheral mononuclear cells.
Article in Journal of clinical immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- Safety and efficacy of IL-23 inhibitors in patients with moderate to severe ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials.International journal of colorectal disease · 2025Pooled it
- DNA methylation is associated with inhaled corticosteroid response in persistent childhood asthmatics.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2019Trial
- Differential connectivity of gene regulatory networks distinguishes corticosteroid response in asthma.The Journal of allergy and clinical immunology · 2018Trial
- Distinct endotypes of steroid-resistant asthma characterized by IL-17A(high) and IFN-γ(high) immunophenotypes: Potential benefits of calcitriol.The Journal of allergy and clinical immunology · 2015Trial
- Metabolic Reprogramming and ILC2 Plasticity in Obesity-related Asthma.Clinical reviews in allergy & immunology · 2026Review
- STING pathway contributes to Steroid-Hyporesponsive Lung Inflammation in DSS-induced colitis mice model.PloS one · 2026Article
- Interleukin-23 in lung and airway diseases: from pathogenesis to precision-guided therapeutic targeting.Frontiers in pharmacology · 2026Review
- Early-life viral infections and asthma: new cells and ideas.Current opinion in pediatrics · 2025Review
- Fueling the fire in the lung-brain axis: The salience network connects allergen-provoked TH17 responses to psychological stress in asthma.Brain, behavior, and immunity · 2025Article
- Glucocorticoid Insensitivity: Is It a Question of Time and Place?Biomedicines · 2025Review
- JAK-STAT pathway, type I/II cytokines, and new potential therapeutic strategy for autoimmune bullous diseases: update on pemphigus vulgaris and bullous pemphigoid.Frontiers in immunology · 2025Review
- Calprotectin is regulated by IL-17A and induces steroid hyporesponsiveness in asthma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Association of Obesity and Severe Asthma in Adults.Journal of clinical medicine · 2024Review
- Systemic Inflammation in Asthma: What Are the Risks and Impacts Outside the Airway?The journal of allergy and clinical immunology. In practice · 2024Review
- Bronchial epithelial transcriptomics and experimental validation reveal asthma severity-related neutrophilc signatures and potential treatments.Communications biology · 2024Article
- Article
- Unraveling heterogeneity and treatment of asthma through integrating multi-omics data.Frontiers in allergy · 2024Review
- Molecular pathways underlying lung-brain axis signaling in asthma: Relevance for psychopathology and neuroinflammation.The Journal of allergy and clinical immunology · 2024Article
- Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.Physiological reviews · 2024Review
- Advancing Treatment in Bullous Pemphigoid: A Comprehensive Review of Novel Therapeutic Targets and Approaches.Clinical reviews in allergy & immunology · 2023Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeMost asthmatic patients have well controlled symptoms with regular treatment, but some require much higher doses of inhaled and oral corticosteroids, or in rare cases fail to respond; these patients may present Th-17 cell infiltration and associated cytokines (IL-17A and -F) in the airways, sputum and peripheral blood. Because glucocorticoid receptor-beta (GR-beta) is associated with corticosteroid resistance, we investigated whether Th-17 associated cytokines induce steroid insensitivity in PBMCs via GR-beta up-regulation.
methodsGR-alpha, GR-beta, GILZ and IL-6 expression were analyzed in PBMCs stimulated with IL-2/IL-4, IL-17A/IL-17F and IL-23 cytokines by quantitative RT-PCR. Dexamethasone-inhibition of PHA-induced proliferation and Dexamethasone-induced apoptosis were determined by either (3)H-thymidine or CFSE-labelled cells and by Annexin-V staining and flow cytometry.
resultsIL-17 and IL-23 cytokines significantly increased GR-beta expression. IL-2/IL-4 significantly decreased GR-alpha expression without affecting GR-beta. IL17, IL-23 and IL2 + 4 stimulations significantly hampered Dexamethasone-inhibition of proliferation (Dex EC(50) for: IL-17A + F = 251 nM; IL-23 = 435 nM; IL2 + 4 = 950 nM; Medium = 90 nM). IL2 + 4 and IL17A + F but not IL-23, significantly hampered Dexamethasone-induced apoptosis (1400 and 320 nM Dex, respectively). Dexamethasone's trans-activation of GILZ and trans-repression of NF-kB-driven IL-6 expression were both inhibited by IL2 + 4; IL17 + IL23 antagonized Dex trans-repression in PBMC from asthmatics.
conclusionsGR-beta up-regulation by IL-17/IL-23 cytokines is associated with induced steroid insensitivity in PBMCs, observed as diminished Dexamethasone's effects on cell proliferation, apoptosis and gene regulation. Steroid resistance induced by IL-2/IL-4 was associated with decreased GR-alpha expression. This study supports the possibility that Th-17 lymphocytes and associated cytokines play a role in the mechanism of steroid hypo-responsiveness in severe asthmatics.
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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.