ArticleThe Journal of allergy and clinical immunology2015
IL-13 desensitizes β2-adrenergic receptors in human airway epithelial cells through a 15-lipoxygenase/G protein receptor kinase 2 mechanism.
Article in The Journal of allergy and clinical immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- 15-LOX-catalytic bias towards ether-(alkenyl)-ETE-PEs oxidation bestows selectivity of PRO-ferroptotic cell death signaling.Nature communications · 2026Article
- IL-13 Modulates Antiviral Effector and Proinflammatory Pathways in Rhinovirus-Infected Pediatric Bronchial Epithelium.bioRxiv : the preprint server for biology · 2025Article
- Unmasking Pediatric Asthma: Epigenetic Fingerprints and Markers of Respiratory Infections.International journal of molecular sciences · 2025Review
- Compartmentalized mitochondrial ferroptosis converges with optineurin-mediated mitophagy to impact airway epithelial cell phenotypes and asthma outcomes.Nature communications · 2024Article
- Rhinovirus C15 Attenuates Relaxation and cAMP Production in Human Airways and Smooth Muscle.American journal of respiratory cell and molecular biology · 2023Article
- Article
- The stimulation and inhibition of beta-2 adrenergic receptor on the inflammatory responses of ovary and immune system in the aged laying hens.BMC veterinary research · 2021Article
- G Protein-Coupled Receptor Kinase 2 (GRK2) Regulates T Cell Response in a Murine Model of House Dust Mite-Induced Asthma.Frontiers in allergy · 2021Article
- Dexamethasone rescues TGF-β1-mediated βRespiratory research · 2020Article
- PEBP1 acts as a rheostat between prosurvival autophagy and ferroptotic death in asthmatic epithelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Predictive significance of arachidonate 15-lipoxygenase for eosinophilic chronic rhinosinusitis with nasal polyps.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2020Article
- 15-Lipoxygenase 1 in nasal polyps promotes CCL26/eotaxin 3 expression through extracellular signal-regulated kinase activation.The Journal of allergy and clinical immunology · 2019Article
- Emerging cellular functions of the lipid metabolizing enzyme 15-Lipoxygenase-1.Cell proliferation · 2018Review
- Preferential Generation of 15-HETE-PE Induced by IL-13 Regulates Goblet Cell Differentiation in Human Airway Epithelial Cells.American journal of respiratory cell and molecular biology · 2017Article
- Reduced suppressive effect of βRespiratory research · 2017Article
- A regulatory role for β-adrenergic receptors regarding the resolvin D1 (RvD1) pathway in the diabetic retina.PloS one · 2017Article
- Inhibition of PI3K promotes dilation of human small airways in a rho kinase-dependent manner.British journal of pharmacology · 2016Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundβ2-Adrenergic receptor (β2AR) agonists are critical treatments for asthma. However, receptor desensitization can lead to loss of therapeutic effects. Although desensitization to repeated use of β2-agonists is well studied, type 2 inflammation could also affect β2AR function.
objectiveWe sought to evaluate the effect of the type 2 cytokine IL-13 on β2AR desensitization in human airway epithelial cells (HAECs) and determine whether 15-lipoxygenase-1 (15LO1) binding with phosphatidylethanolamine-binding protein 1 (PEBP1) contributes to desensitization through release of G protein receptor kinase 2 (GRK2).
methodsHAECs in air-liquid interface culture with or without IL-13 (48 hours) or isoproterenol hydrochloride (ISO; 30 minutes) pretreatment were stimulated with ISO (10 minutes). Cyclic adenosine 3, 5-monophosphate (cAMP) levels were measured using ELISA, and β2AR and GRK2 phosphorylation was measured using Western blotting. Short interfering RNA was used for 15LO1 knockdown. Interactions of GRK2, PEBP1, and 15LO1 were detected by means of immunoprecipitation/Western blotting and immunofluorescence. HAECs and airway tissue from control subjects and asthmatic patients were evaluated for I5LO1, PEBP1, and GRK2.
resultsPretreatment with ISO or IL-13 decreased ISO-induced cAMP generation compared with ISO for 10 minutes alone paralleled by increases in β2AR and GRK2 phosphorylation. GRK2 associated with PEBP1 after 10 minutes of ISO in association with low phosphorylated GRK2 (pGRK2) levels. In contrast, in the presence of IL-13 plus ISO (10 minutes), binding of GRK2 to PEBP1 decreased, whereas 15LO1 binding and pGRK2 levels increased. 15LO1 knockdown restored ISO-induced cAMP generation. These findings were recapitulated in freshly brushed HAECs from cells and tissue of asthmatic patients.
conclusionIL-13 treatment of HAECs leads to β2AR desensitization, which involves 15LO1/PEBP1 interactions to free GRK2, and allows it to phosphorylate (and desensitize) β2ARs, suggesting that the beneficial effects of β2-agonists could be blunted in patients with type 2 associated 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.