Azithromycin ameliorates sulfur dioxide-induced airway epithelial damage and inflammatory responses
- PDF / 3,416,455 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 98 Downloads / 161 Views
RESEARCH
Open Access
Azithromycin ameliorates sulfur dioxideinduced airway epithelial damage and inflammatory responses Jon Petur Joelsson1,2, Jennifer A. Kricker1,2, Ari J. Arason1,2,3, Snaevar Sigurdsson4, Bryndis Valdimarsdottir1,2, Fridrik Runar Gardarsson2, Clive P. Page2,5, Fredrik Lehmann2, Thorarinn Gudjonsson1,3,2 and Saevar Ingthorsson1,2,6*
Abstract Background: The airway epithelium (AE) forms the first line of defence against harmful particles and pathogens. Barrier failure of the airway epithelium contributes to exacerbations of a range of lung diseases that are commonly treated with Azithromycin (AZM). In addition to its anti-bacterial function, AZM has immunomodulatory effects which are proposed to contribute to its clinical effectiveness. In vitro studies have shown the AE barrier-enhancing effects of AZM. The aim of this study was to analyze whether AE damage caused by inhalation of sulfur dioxide (SO2) in a murine model could be reduced by pre-treatment with AZM. Methods: The leakiness of the AE barrier was evaluated after SO2 exposure by measuring levels of human serum albumin (HSA) in bronchoalveolar lavage fluid (BALF). Protein composition in BALF was also assessed and lung tissues were evaluated across treatments using histology and gene expression analysis. Results: AZM pre-treatment (2 mg/kg p.o. 5 times/week for 2 weeks) resulted in reduced glutathione-S-transferases in BALF of SO2 injured mice compared to control (without AZM treatment). AZM treated mice had increased intracellular vacuolization including lamellar bodies and a reduction in epithelial shedding after injury in addition to a dampened SO2-induced inflammatory response. Conclusions: Using a mouse model of AE barrier dysfunction we provide evidence for the protective effects of AZM in vivo, possibly through stabilizing the intracellular microenvironment and reducing inflammatory responses. Our data provide insight into the mechanisms contributing to the efficacy of AZM in the treatment of airway diseases. Keywords: Azithromycin, Immunomodulation, Lung barrier enhancement, Glutathione-S-transferase, Lamellar bodies
Background Environmental pollutants are often associated with exacerbation of disease, including those linked to cardiac, skin and respiratory conditions [1, 2]. Air pollution is comprised of several components, one of the major ones being sulfur dioxide (SO2), a gas commonly produced * Correspondence: [email protected] 1 Stem Cell Research Unit, BioMedical Center, School of Health Sciences, University of Iceland, Reykjavík, Iceland 2 EpiEndo Pharmaceuticals, Reykjavík, Iceland Full list of author information is available at the end of the article
from combustion of sulfur-containing fuels such as coal as well as from volcanic eruptions [3]. Fine particles formed from fugitive dust, SO2 and oxygen result in particulate matter (PM), a primary pollutant and irritant which, as air pollution increases, leads to an increase in respiratory and cardiovascular diseases [1]. The lungs, lined with an epithelial layer, are compl
Data Loading...
