ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Functional KCa3.1 channels regulate steroid insensitivity in bronchial smooth muscle cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Trial
- Integrating GPCR Regulation and Calcium Dynamics in Airway Smooth Muscle Function: A Comprehensive Review.Cells · 2026Review
- Effects ofPlants (Basel, Switzerland) · 2023Article
- Group 3 innate lymphoid cells secret neutrophil chemoattractants and are insensitive to glucocorticoid via aberrant GR phosphorylation.Respiratory research · 2023Article
- The chemokine CX3CL1/fractalkine regulates immunopathogenesis during fungal-associated allergic airway inflammation.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Insights into glucocorticoid responses derived from omics studies.Pharmacology & therapeutics · 2021Review
- Human Lung Mast Cells Impair Corticosteroid Responsiveness in Human Airway Smooth Muscle Cells.Frontiers in allergy · 2021Article
- KCa3.1 Mediates Dysregulation of Mitochondrial Quality Control in Diabetic Kidney Disease.Frontiers in cell and developmental biology · 2021Article
- 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
- CaBritish journal of pharmacology · 2020Review
- The Potassium Channel Odyssey: Mechanisms of Traffic and Membrane Arrangement.International journal of molecular sciences · 2019Review
- The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma.Frontiers in pharmacology · 2019Review
- Increased β2-adrenoceptor phosphorylation in airway smooth muscle in severe asthma: possible role of mast cell-derived growth factors.Clinical and experimental immunology · 2018Article
- Fractalkine/CX3CR1 Contributes to Endometriosis-Induced Neuropathic Pain and Mechanical Hypersensitivity in Rats.Frontiers in cellular neuroscience · 2018Article
- Modulation of Retrograde Trafficking of KCa3.1 in a Polarized Epithelium.Frontiers in physiology · 2017Article
- Reslizumab and Eosinophilic Asthma: One Step Closer to Precision Medicine?Frontiers in immunology · 2017Review
- Protein phosphatase 5 mediates corticosteroid insensitivity in airway smooth muscle in patients with severe asthma.Allergy · 2017Article
- Developmental conditioning of endothelium-derived hyperpolarizing factor-mediated vasorelaxation.Journal of hypertension · 2016Article
- Effect of the plant derivative Compound A on the production of corticosteroid-resistant chemokines in airway smooth muscle cells.American journal of respiratory cell and molecular biology · 2015Article
- Orai/CRACM1 and KCa3.1 ion channels interact in the human lung mast cell plasma membrane.Cell communication and signaling : CCS · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Identifying the factors responsible for relative glucocorticosteroid (GC) resistance present in patients with severe asthma and finding tools to reverse it are of paramount importance. In asthma we see in vivo evidence of GC-resistant pathways in airway smooth muscle (ASM) bundles that can be modeled in vitro by exposing cultured ASM cells to TNF-α/IFN-γ. This action drives GC insensitivity via protein phosphatase 5-dependent impairment of GC receptor phosphorylation. In this study, we investigated whether KCa3.1 ion channels modulate the activity of GC-resistant pathways using our ASM model of GC insensitivity. Immunohistochemical staining of endobronchial biopsies revealed that KCa3.1 channels are localized to the plasma membrane and nucleus of ASM in both healthy controls and asthmatic patients, irrespective of disease severity. Western blot assays and immunofluorescence staining confirmed the nuclear localization of KCa3.1 channels in ASM cells. The functional importance of KCa3.1 channels in the regulation of GC-resistant chemokines induced by TNF-α/IFN-γ was assessed using complementary inhibitory strategies, including KCa3.1 blockers (TRAM-34 and ICA-17043) or KCa3.1-specific small hairpin RNA delivered by adenoviruses. KCa3.1 channel blockade led to a significant reduction of fluticasone-resistant CX3CL1, CCL5, and CCL11 gene and protein expression. KCa3.1 channel blockade also restored fluticasone-induced GC receptor-α phosphorylation at Ser(211) and transactivation properties via the suppression of cytokine-induced protein phosphatase 5 expression. The effect of KCa3.1 blockade was evident in ASM cells from both healthy controls and asthmatic subjects. In summary, KCa3.1 channels contribute to the regulation of GC-resistant inflammatory pathways in ASM cells: blocking KCa3.1 channels may enhance corticosteroid activity in severe asthma.
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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.