ArticlePloS one2012
Restoration of corticosteroid sensitivity by p38 mitogen activated protein kinase inhibition in peripheral blood mononuclear cells from severe asthma.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 102 citations in OpenAlex.
- HFA-BDP Metered-Dose Inhaler Exhaled Through the Nose Improves Eosinophilic Chronic Rhinosinusitis With Bronchial Asthma: A Blinded, Placebo-Controlled Study.Frontiers in immunology · 2018Trial
- How post-translational modifications impact glucocorticoid receptor function in human pathologies.Cell communication and signaling : CCS · 2026Review
- By what molecular mechanisms do social determinants impact cardiometabolic risk?Clinical science (London, England : 1979) · 2023Review
- Glucocorticoid Insensitivity in Asthma: The Unique Role for Airway Smooth Muscle Cells.International journal of molecular sciences · 2022Review
- Crosstalk between p38 MAPK and GR Signaling.International journal of molecular sciences · 2022Review
- Conditioned medium from human tonsil-derived mesenchymal stem cells inhibits glucocorticoid-induced adipocyte differentiation.PloS one · 2022Article
- Marine-Derived Compounds for the Potential Treatment of Glucocorticoid Resistance in Severe Asthma.Marine drugs · 2021Review
- Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD.Antioxidants (Basel, Switzerland) · 2021Review
- Dexamethasone and p38 MAPK inhibition of cytokine production from human lung fibroblasts.Fundamental & clinical pharmacology · 2021Article
- Review
- Insights into glucocorticoid responses derived from omics studies.Pharmacology & therapeutics · 2021Review
- Potential Role of Mast Cells in Regulating Corticosteroid Insensitivity in Severe Asthma.Advances in experimental medicine and biology · 2021Article
- Why do some asthma patients respond poorly to glucocorticoid therapy?Pharmacological research · 2020Review
- Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease.British journal of pharmacology · 2020Article
- Long non-coding RNA growth arrest specific-5: a potential biomarker for early diagnosis of severe asthma.Journal of thoracic disease · 2020Article
- Interleukin-35 sensitizes monocytes from patients with asthma to glucocorticoid therapy by regulating p38 MAPK.Experimental and therapeutic medicine · 2020Article
- P38 MAPK and glucocorticoid receptor crosstalk in bronchial epithelial cells.Journal of molecular medicine (Berlin, Germany) · 2020Article
- LABAs and p38MAPK Inhibitors Reverse the Corticosteroid-Insensitivity of IL-8 in Airway Smooth Muscle Cells of COPD.Journal of clinical medicine · 2019Article
- IL-2 modulates Th2 cell responses to glucocorticosteroid: A cause of persistent type 2 inflammation?Immunity, inflammation and disease · 2019Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSevere asthma accounts for a small number of asthmatics but represents a disproportionate cost to health care systems. The underlying mechanism in severe asthma remains unknown but several mechanisms are likely to be involved because of a very heterogeneous profile. We investigated the effects of a p38MAPK inhibitor in corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) from severe asthmatics and the profile of its responders. METHODOLOGY/PRINCIPAL
findingsCorticosteroid sensitivity was determined by measuring dexamethasone inhibition of CD3/28 and TNF-α induced IL-8 production in PBMCs by using ELISA. PBMCs from severe asthmatics were relatively less sensitive to dexamethasone (Dex) as compared to those of non-severe asthmatics and healthy volunteers. The IC(50) values of Dex negatively correlated with decreased glucocorticoid receptor (GR) nuclear translocation assessed using immunocytochemistry (r = -0.65; p<0.0005) and with decreased FEV(1) (% predicted) (r = 0.6; p<0.0005). A p38α/β inhibitor (SB203580) restored Dex-sensitivity in a subpopulation of severe asthma that was characterized by a defective GR nuclear translocation, clinically by lower FEV(1) and higher use of oral prednisolone. We also found that SB203580 partially inhibited GR phosphorylation at serine 226, resulting in increased GR nuclear translocation in IL-2/IL-4 treated corticosteroid insensitive U937s. CONCLUSIONS/SIGNIFICANCE: p38MAPKα/β is involved in defective GR nuclear translocation due to phosphorylation at Ser226 and this will be a useful biomarker to identify responders to p38MAPKα/β inhibitor in the future.
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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.