MiR-17 overexpression in cystic fibrosis airway epithelial cells decreases interleukin-8 production

Interleukin (IL)-8 levels are higher than normal in cystic fibrosis (CF) airways, causing neutrophil infiltration and non-resolving inflammation. Overexpression of microRNAs that target IL-8 expression in airway epithelial cells may represent a therapeutic strategy for cystic fibrosis. - IL-8 protei...

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Hauptverfasser: Oglesby, Irene K. (VerfasserIn) , Vencken, Sebastian F. (VerfasserIn) , Agrawal, Raman (VerfasserIn) , Gaughan, Kevin (VerfasserIn) , Molloy, Kevin (VerfasserIn) , Higgins, Gerard (VerfasserIn) , McNally, Paul (VerfasserIn) , McElvaney, Noel G. (VerfasserIn) , Mall, Marcus A. (VerfasserIn) , Greene, Catherine M. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: July 09 2015
In: The European respiratory journal
Year: 2015, Jahrgang: 46, Heft: 5, Pages: 1350-1360
ISSN:1399-3003
DOI:10.1183/09031936.00163414
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1183/09031936.00163414
Verlag, lizenzpflichtig, Volltext: https://erj.ersjournals.com/content/46/5/1350
Volltext
Verfasserangaben:Irene K. Oglesby, Sebastian F. Vencken, Raman Agrawal, Kevin Gaughan, Kevin Molloy, Gerard Higgins, Paul McNally, Noel G. McElvaney, Marcus A. Mall and Catherine M. Greene
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Zusammenfassung:Interleukin (IL)-8 levels are higher than normal in cystic fibrosis (CF) airways, causing neutrophil infiltration and non-resolving inflammation. Overexpression of microRNAs that target IL-8 expression in airway epithelial cells may represent a therapeutic strategy for cystic fibrosis. - IL-8 protein and mRNA were measured in cystic fibrosis and non-cystic fibrosis bronchoalveolar lavage fluid and bronchial brushings (n=20 per group). miRNAs decreased in the cystic fibrosis lung and predicted to target IL-8 mRNA were quantified in βENaC-transgenic, cystic fibrosis transmembrane conductance regulator (Cftr)-/- and wild-type mice, primary cystic fibrosis and non-cystic fibrosis bronchial epithelial cells and a range of cystic fibrosis versus non-cystic fibrosis airway epithelial cell lines or cells stimulated with lipopolysaccharide, Pseudomonas-conditioned medium or cystic fibrosis bronchoalveolar lavage fluid. The effect of miRNA overexpression on IL-8 protein production was measured. - miR-17 regulates IL-8 and its expression was decreased in adult cystic fibrosis bronchial brushings, βENaC-transgenic mice and bronchial epithelial cells chronically stimulated with Pseudomonas-conditioned medium. Overexpression of miR-17 inhibited basal and agonist-induced IL-8 protein production in F508del-CFTR homozygous CFTE29o− tracheal, CFBE41o− and/or IB3 bronchial epithelial cells. - These results implicate defective CFTR, inflammation, neutrophilia and mucus overproduction in regulation of miR-17. Modulating miR-17 expression in cystic fibrosis bronchial epithelial cells may be a novel anti-inflammatory strategy for cystic fibrosis and other chronic inflammatory airway diseases. - Tweetable abstract ERSpublications - click to tweetOverexpression of miR-17 in cystic fibrosis airway epithelial cells decreases interleukin-8 protein production http://ow.ly/MZbXB
Beschreibung:Gesehen am 22.06.2020
Beschreibung:Online Resource
ISSN:1399-3003
DOI:10.1183/09031936.00163414