Novel effects of azithromycin on tight junction proteins in human airway epithelia.
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.
Asgrimsson
Valthor
V
Faculty of Medicine, Landspitali University Hospital, Fossvogi E7, 108 Reykjavik, Iceland.
Gudjonsson
Thorarinn
T
Gudmundsson
Gudmundur Hrafn
GH
Baldursson
Olafur
O
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology*; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D062445:Claudin-1; D062506:Claudin-4; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D062726:Junctional Adhesion Molecules; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D000900:Anti-Bacterial Agents; C568108:CLDN1 protein, human; C568157:CLDN4 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D062445:Claudin-1; D062506:Claudin-4; D062726:Junctional Adhesion Molecules; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D017963:Azithromycin