ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
IL-8 inhibits cAMP-stimulated alveolar epithelial fluid transport via a GRK2/PI3K-dependent mechanism.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
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- Plasma-derived extracellular vesicles prime alveolar macrophages for autophagy and ferroptosis in sepsis-induced acute lung injury.Molecular medicine (Cambridge, Mass.) · 2025Article
- A narrative review of chemokine receptors CXCR1 and CXCR2 and their role in acute respiratory distress syndrome.European respiratory review : an official journal of the European Respiratory Society · 2024Review
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- Phosphodiesterase 4 mediates interleukin-8-induced heterologous desensitization of the βFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
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- Lycopene Inhibits Toll-Like Receptor 4-Mediated Expression of Inflammatory Cytokines in House Dust Mite-Stimulated Respiratory Epithelial Cells.Molecules (Basel, Switzerland) · 2021Article
- G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases.Frontiers in immunology · 2021Review
- A prospective investigation of interleukin-8 levels in pediatric acute respiratory failure and acute respiratory distress syndrome.Critical care (London, England) · 2019Article
- Effects of inflammatory factors including plasma tumor necrosis factor-α in the clinical treatment of acute respiratory distress syndrome.Oncology letters · 2017Article
- Cytokine-Ion Channel Interactions in Pulmonary Inflammation.Frontiers in immunology · 2017Review
- Cytokine-Regulation of NaFrontiers in immunology · 2017Review
- Inflammatory Responses Regulating Alveolar Ion Transport during Pulmonary Infections.Frontiers in immunology · 2017Review
- The Lectin-like Domain of TNF Increases ENaC Open Probability through a Novel Site at the Interface between the Second Transmembrane and C-terminal Domains of the α-Subunit.The Journal of biological chemistry · 2016Article
- Adrenergic signaling in heart failure and cardiovascular aging.Maturitas · 2016Review
- Epithelial Anion Transport as Modulator of Chemokine Signaling.Mediators of inflammation · 2016Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Patients with acute lung injury (ALI) who retain maximal alveolar fluid clearance (AFC) have better clinical outcomes. Experimental and small clinical studies have shown that β2-adrenergic receptor (β2AR) agonists enhance AFC via a cAMP-dependent mechanism. However, two multicenter phase 3 clinical trials failed to show that β2AR agonists provide a survival advantage in patients with ALI. We hypothesized that IL-8, an important mediator of ALI, directly antagonizes the alveolar epithelial response to β2AR agonists. Short-circuit current and whole-cell patch-clamping experiments revealed that IL-8 or its rat analog CINC-1 decreases by 50% β2AR agonist-stimulated vectorial Cl(-) and net fluid transport across rat and human alveolar epithelial type II cells via a reduction in the cystic fibrosis transmembrane conductance regulator activity and biosynthesis. This reduction was mediated by heterologous β2AR desensitization and down-regulation (50%) via the G-protein-coupled receptor kinase 2 (GRK2)/PI3K signaling pathway. Inhibition of CINC-1 restored β2AR agonist-stimulated AFC in an experimental model of ALI in rats. Finally, consistent with the experimental results, high pulmonary edema fluid levels of IL-8 (>4000 pg/ml) were associated with impaired AFC in patients with ALI. These results demonstrate a novel role for IL-8 in inhibiting β2AR agonist-stimulated alveolar epithelial fluid transport via GRK2/PI3K-dependent mechanisms.-Roux, J., McNicholas, C. M., Carles, M., Goolaerts, A., Houseman, B. T., Dickinson, D. A., Iles, K. E., Ware, L. B., Matthay, M. A., Pittet, J.-F. IL-8 inhibits cAMP-stimulated alveolar epithelial fluid transport via a GRK2/PI3K-dependent mechanism.
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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.