ArticleMolecular pharmacology2011
p38 mitogen-activated protein kinase-γ inhibition by long-acting β2 adrenergic agonists reversed steroid insensitivity in severe asthma.
Article in Molecular pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 65 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
- Comparison of Tylophora indica with Tylophora pauciflora coupled with network pharmacology of phenanthroindolizidine alkaloids sheds light on its antiallergic potential.Molecular biology reports · 2026Article
- Glucocorticoid Insensitivity in Asthma: The Unique Role for Airway Smooth Muscle Cells.International journal of molecular sciences · 2022Review
- An endothelial proinflammatory phenotype precedes the development of the engraftment syndrome after autologous Hct.Bone marrow transplantation · 2022Article
- Crosstalk between p38 MAPK and GR Signaling.International journal of molecular sciences · 2022Review
- Inhibition of Spleen Tyrosine Kinase Restores Glucocorticoid Sensitivity to Improve Steroid-Resistant Asthma.Frontiers in pharmacology · 2022Article
- Why do some asthma patients respond poorly to glucocorticoid therapy?Pharmacological research · 2020Review
- LABAs and p38MAPK Inhibitors Reverse the Corticosteroid-Insensitivity of IL-8 in Airway Smooth Muscle Cells of COPD.Journal of clinical medicine · 2019Article
- Regulation of Interaction between the Upper and Lower Airways in United Airway Disease.Medical sciences (Basel, Switzerland) · 2019Review
- Reduced suppressive effect of βRespiratory research · 2017Article
- Glucocorticoid-independent modulation of GR activity: Implications for immunotherapy.Pharmacology & therapeutics · 2016Review
- Protein tyrosine phosphatase PTP-RR regulates corticosteroid sensitivity.Respiratory research · 2016Article
- Restoration of Corticosteroid Sensitivity in Chronic Obstructive Pulmonary Disease by Inhibition of Mammalian Target of Rapamycin.American journal of respiratory and critical care medicine · 2016Article
- Corticosteroid insensitive alveolar macrophages from asthma patients; synergistic interaction with a p38 mitogen-activated protein kinase (MAPK) inhibitor.British journal of clinical pharmacology · 2015Article
- Accumulation of cytoplasmic glucocorticoid receptor is related to elevation of FKBP5 in lymphocytes of depressed patients.Journal of molecular neuroscience : MN · 2015Article
- Article
- Impaired nuclear translocation of the glucocorticoid receptor in corticosteroid-insensitive airway smooth muscle in severe asthma.American journal of respiratory and critical care medicine · 2015Article
- Basal p38 mitogen-activated protein kinase regulates unliganded glucocorticoid receptor function in airway smooth muscle cells.American journal of respiratory cell and molecular biology · 2014Article
- Glucocorticoid sensitivity in health and disease.Nature reviews. Endocrinology · 2013Review
- A novel macrolide/fluoroketolide, solithromycin (CEM-101), reverses corticosteroid insensitivity via phosphoinositide 3-kinase pathway inhibition.British journal of pharmacology · 2013Article
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6 authors at 1 institution in 1 country.
Funding
Abstract
Corticosteroid insensitivity (CI) is a major barrier to treating severe asthma. Despite intensive research, the molecular mechanism of CI remains uncertain. The aim of this study was to determine abnormality in corticosteroid action in severe asthma and to identify the molecular mechanism of the long-acting β(2)-adrenergic agonists (LABAs) formoterol and salmeterol on restoration of corticosteroid sensitivity in severe asthma in vitro. Peripheral blood mononuclear cells (PBMCs) were obtained from 16 subjects with severe corticosteroid-insensitive asthma, 6 subjects with mild corticosteroid-sensitive asthma, and 11 healthy volunteers. Corticosteroid (dexamethasone) sensitivity was determined on tumor necrosis factor-α (TNF-α)-induced interleukin (IL)-8 production. Glucocorticoid receptor (GR) phosphorylation and kinase phosphorylation were evaluated by immunoprecipitation-Western blotting analysis and kinase phosphorylation array in IL-2/IL-4-treated corticosteroid insensitive model in PBMCs. In vitro corticosteroid sensitivity on TNF-α-induced IL-8 production was significantly lower in patients with severe asthma than in healthy volunteers and patients with mild asthma. This CI seen in severe asthma was associated with reduced GR nuclear translocation and with hyperphosphorylation of GR, which were reversed by LABAs. In IL-2/IL-4-treated PBMCs, LABAs inhibited phosphorylation of Jun-NH(2)-terminal kinase and p38 mitogen-activated protein kinase-γ (p38MAPK-γ) as well as GR. In addition, cells with p38MAPK-γ knockdown by RNA interference did not develop CI in the presence of IL-2/IL-4. Furthermore, p38MAPK-γ protein expression was up-regulated in PBMCs from some patients with severe asthma. In conclusion, p38 MAPK-γ activation impairs corticosteroid action and p38 MAPK-γ inhibition by LABAs has potential for the treatment of 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.