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Lookup NU author(s): Adillah Binti Yusof,
Dr Ian Forrest,
Emeritus Professor Nick Europe-Finner,
Professor Andrew FisherORCiD,
Emeritus Professor Tim Cawston,
Dr James Lordan,
Professor Christopher WardORCiD
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BackgroundThe bronchial epithelium is a source of mediators that may play a role in the airway inflammation and remodeling of post-transplant obliterative bronchiolitis (OB). Traditional strategies have failed to have an impact on OB. Recent studies have suggested a role for azithromycin in managing the condition. In this study we aimed to determine the effect of azithromycin on LPS-mediated epithelial release of factors relevant to airway neutrophilia and remodeling in a unique population of primary bronchial epithelial cells (PBECs) derived from stable lung allografts. MethodsPBECs were established from bronchial brushings of stable lung transplant recipients and treated with lipopolysaccharide (LPS, 0.1, 1 and 10 μg/ml) for 48 hours. Interleukin-8 (IL-8), granulocyte macrophage colony-stimulating factor (GM-CSF) and vascular endothelial growth factor (VEGF) protein levels were measured by Luminex analyzer. PBECs were then incubated with LPS and azithromycin, and protein levels were again determined. ResultsLPS caused a significant increase in IL-8 and GM-CSF at concentrations of 1 and 10 μg/ml, with no effect on VEGF release. Azithromycin caused a significant decrease in the LPS-stimulated IL-8 and GM-CSF release. ConclusionsLPS upregulates release of IL-8 and GM-CSF from PBECs derived from stable lung allografts. Sub-microbicidal concentrations of azithromycin attenuate this and may, therefore, alleviate infection-driven neutrophilic airway inflammation and remodeling in the allograft airway.
Author(s): Murphy DM, Forrest IA, Corris PA, Johnson GE, Small T, Jones D, Fisher AJ, Egan JJ, Cawston TE, Lordan JL, Ward C
Publication type: Article
Publication status: Published
Journal: The Journal of Heart and Lung Transplantation
ISSN (print): 1053-2498
ISSN (electronic): 1557-3117
Publisher: Elsevier Inc.
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