ArticleThe Journal of allergy and clinical immunology2010
Mechanism of glucocorticoid protection of airway smooth muscle from proasthmatic effects of long-acting beta2-adrenoceptor agonist exposure.
Article in The Journal of allergy and clinical immunology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Evolutionary Integration and Glucocorticoid Regulation of the Respiratory System: Structure, Function, and Homeostatic Adaptation.Medical sciences (Basel, Switzerland) · 2026Review
- Homeostatic glucocorticoid signaling in airway smooth muscle: A roadmap to asthma pathogenesis.Frontiers in endocrinology · 2022Article
- Dexamethasone rescues TGF-β1-mediated βRespiratory research · 2020Article
- The use of βERJ open research · 2020Review
- 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
- Article
- βScientific reports · 2017Article
- Understanding how long-acting βBritish journal of pharmacology · 2016Review
- Differentiation of human bronchial epithelial cells: role of hydrocortisone in development of ion transport pathways involved in mucociliary clearance.American journal of physiology. Cell physiology · 2016Article
- Asthma Pharmacogenomics: 2015 Update.Current allergy and asthma reports · 2015Review
- Salmeterol Efficacy and Bias in the Activation and Kinase-Mediated Desensitization of β2-Adrenergic Receptors.Molecular pharmacology · 2015Article
- Article
- Article
- Construction of a cell model of β2-adrenoceptor downregulation.Journal of thoracic disease · 2013Article
- IL-13-induced changes in endogenous glucocorticoid metabolism in the lung regulate the proasthmatic response.American journal of physiology. Lung cellular and molecular physiology · 2012Article
- G Protein βγ-subunit signaling mediates airway hyperresponsiveness and inflammation in allergic asthma.PloS one · 2012Article
- The pharmacogenetics and pharmacogenomics of asthma therapy.The pharmacogenomics journal · 2011Review
- A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression.Respiratory research · 2011Article
- Beta-agonist-associated reduction in RGS5 expression promotes airway smooth muscle hyper-responsiveness.The Journal of biological chemistry · 2011Article
- Scientific rationale for the use of alpha-adrenergic agonists and glucocorticoids in the therapy of pediatric stridor.International journal of otolaryngology · 2011Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundChronic use of long-acting beta2-adrenergic receptor agonists (LABAs), resulting in beta2-adrenergic receptor desensitization, has been associated with increased asthma morbidity. When LABAs are used in combination with inhaled glucocorticoids, however, asthma control is improved, raising the following question: Do glucocorticoids inhibit the proasthmatic mechanism that mediates altered contractility in LABA-exposed airway smooth muscle (ASM)?
objectiveThis study aimed to identify the potential protective role and mechanism of action of glucocorticoids in mitigating the effects of prolonged LABA exposure on ASM constrictor and relaxation responsiveness.
methodsCultured human ASM cells and isolated rabbit ASM tissues were examined for induced changes in agonist-mediated cyclic adenosine monophosphate accumulation, constrictor and relaxation responsiveness, and expression of specific glucocorticoid-regulated molecules after 24-hour exposure to the LABA salmeterol in the absence and presence of dexamethasone.
resultsSalmeterol-exposed ASM exhibited impaired cyclic adenosine monophosphate and relaxation responses to isoproterenol and increased acetylcholine-induced contractility. These proasthmatic effects of prolonged LABA exposure were attributed to upregulated phosphodiesterase 4 (PDE4) activity and were ablated by pretreatment with dexamethasone. Further studies demonstrated that (1) dexamethasone suppressed activation of the mitogen-activated protein kinases extracellular signal-regulated kinases 1 and 2 (ERK1/2), which upregulate PDE4 expression in salmeterol-exposed ASM; and (2) the inhibitory actions of dexamethasone on salmeterol-induced ERK1/2 activation and resultant PDE4-mediated changes in ASM responsiveness were prevented by gene silencing or pharmacologic inhibition of dexamethasone-induced expression of mitogen-activated protein kinase phosphatase 1, an endogenous deactivator of ERK1/2 signaling.
conclusionGlucocorticoids prevent the adverse proasthmatic effects of prolonged LABA exposure on airway responsiveness as a result of glucocorticoid-induced upregulation of mitogen-activated protein kinase phosphatase 1, which inhibits proasthmatic ERK1/2 signaling in the LABA-exposed ASM.
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