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Antimicrobial Agents and Chemotherapy, May 2006, p. 1805-1812, Vol. 50, No. 5
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.5.1805-1812.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Novel Effects of Azithromycin on Tight Junction Proteins in Human Airway Epithelia

Valthor Asgrimsson,1,4 Thorarinn Gudjonsson,1,4 Gudmundur Hrafn Gudmundsson,3 and Olafur Baldursson1,2,5*

Faculty of Medicine,1 Faculty of Pharmacy,2 Department of Biology, University of Iceland,3 Icelandic Cancer Society Molecular and Cell Research Laboratory,4 Department of Pulmonary Medicine, Landspitali University Hospital, Reykjavik, Iceland5

Received 16 August 2005/ Returned for modification 18 October 2005/ Accepted 2 March 2006

The macrolide antibiotic azithromycin improves lung function and prognosis among patients with cystic fibrosis or diffuse panbronchiolitis, independently of bacterial eradication. Anti-inflammatory effects have been implicated, but data from in vivo studies are scarce, and the link between abnormal electrolyte content in airway surface liquid and bronchial infections remains uncertain.

In the present study, we treated human airway epithelia on filter supports with azithromycin and monitored transepithelial electrical resistance. We found that azithromycin increased transepithelial electrical resistance of airway epithelia in a dose-dependent manner. Immunocytochemistry and Western blotting showed that addition of azithromycin changed the locations of proteins in cell cultures and induced processing of the tight junction proteins claudin-1 and claudin-4, occludin, and junctional adhesion molecule-A. These effects were reversible, and no effect was seen when cells were treated with penicillin or erythromycin. The data indicate that azithromycin increases the transepithelial electrical resistance of human airway epithelia by changing the processing of tight junction proteins. The results are novel and may help explain the beneficial effects of azithromycin in patients with cystic fibrosis, diffuse panbronchiolitis, and community-acquired pneumonia.

* Corresponding author. Mailing address: Landspitali University Hospital, Fossvogi E7, 108 Reykjavik, Iceland. Phone: 354 824 5735. Fax: 354 543 6568. E-mail: olafbald{at}lsh.is.

Antimicrobial Agents and Chemotherapy, May 2006, p. 1805-1812, Vol. 50, No. 5
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.5.1805-1812.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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