Airway epithelial integrity is protected by a long-acting beta2-adrenergic receptor agonist.
Airway epithelial integrity may be impaired by bacterial exoproducts, which are able to degrade tight junction-associated proteins such as zonula occludens 1 (ZO-1). We have investigated the protective effect of salmeterol, a long-acting beta(2)-adrenergic agonist, on Pseudomonas aeruginosa-induced alteration of the epithelial junctional barrier. We demonstrate in human airway epithelial cells (HAEC) that salmeterol induces a time-dependent increase in ZO-1 protein, although no significant change in ZO-1 transcripts was observed. When HAEC cultures were exposed to P. aeruginosa (PAO1) supernatants, apical expression of ZO-1 protein was maintained in salmeterol-pretreated HAEC cultures, whereas it disappeared after PAO1 exposure in cultures not pretreated with salmeterol. Western blot experiments showed that the 220-kD ZO-1 protein was decreased after PAO1 incubation but was still present in salmeterol-pretreated HAEC extracts. The functional activity of ZO-1 protein was monitored by measuring transepithelial resistance and analyzing the diffusion of a low molecular weight tracer through the intercellular spaces. After PAO1 incubation, the epithelial integrity of HAEC was impaired, as shown by a decrease in transepithelial resistance and increased paracellular permeability, but was not significantly altered after salmeterol preincubation. These results demonstrate that salmeterol may contribute to the protection of the airway epithelium barrier against bacterial virulence factors.
Coraux
Christelle
C
INSERM UMRS 514 and EA 2070, IFR 53, Laboratoire de Pharmacologie, Centre Hospitalier Universitaire Maison Blanche, Reims, France.
Kileztky
Claire
C
Polette
Myriam
M
Hinnrasky
Jocelyne
J
Zahm
Jean-Marie
JM
Devillier
Philippe
P
De Bentzmann
Sophie
S
Puchelle
Edith
E
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D018929:Cell Culture Techniques; D002457:Cell Extracts / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival; D017077:Culture Media, Conditioned / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D000068299:Salmeterol Xinafoate; D062826:Zonula Occludens-1 Protein
D000318:Adrenergic beta-Agonists; D002457:Cell Extracts; D017077:Culture Media, Conditioned; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D000068299:Salmeterol Xinafoate; D000242:Cyclic AMP; D000420:Albuterol