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Azithromycin attenuates effects of lipopolysaccharide on lung allograft bronchial epithelial cells

Lookup NU author(s): Adillah Binti Yusof, Dr Ian Forrest, Professor Paul Corris, Therese Small, Debra Jones, Professor Andrew Fisher, Emeritus Professor Tim Cawston, Dr James Lordan, Dr Christopher Ward

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Abstract

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.


Publication metadata

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

Year: 2008

Volume: 27

Issue: 11

Pages: 1210-6

ISSN (print): 1053-2498

ISSN (electronic): 1557-3117

Publisher: Elsevier Inc.

URL: http://dx.doi.org/10.1016/j.healun.2008.07.026

DOI: 10.1016/j.healun.2008.07.026


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