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Published ahead of print on October 3, 2003, doi:10.1165/rcmb.2003-0056OC

Am. J. Respir. Cell Mol. Biol., Volume 30, Number 5, May 2004, 605-612

A more recent version of this article appeared on May 1, 2004
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Submitted on February 19, 2003
Revised on September 25, 2003

AIRWAY EPITHELIAL INTEGRITY IS PROTECTED BY A LONG-ACTING {beta}2-ADRENERGIC RECEPTOR AGONIST

Christelle CORAUX1, Claire KILEZTKY1, Myriam POLETTE1, Jocelyne HINNRASKY1, Jean-Marie ZAHM1, Philippe DEVILLIER2, Sophie de BENTZMANN1, and Edith PUCHELLE1*

1 UMRS 514, INSERM, REIMS, France, 2 EA 2070 (Laboratoire de Pharmacologie), UNIVERSITE, REIMS, France

* To whom correspondence should be addressed. E-mail: epuche{at}worldnet.fr.

Airway epithelial integrity may be impaired by bacterial exoproducts which are able to degrade tight junction (TJ)-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 (P. 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 ZO-1 protein was maintained in salmeterol pre-treated HAEC cultures, whereas it disappeared after PAO1 exposure in cultures not pre-treated with salmeterol. Western blot experiments showed that the 220 kD ZO-1 protein was decreased after PAO1 incubation but was still present in salmeterol pre-treated HAEC extracts. The functional activity of ZO-1 protein was monitored by measuring transepithelial resistance (TER) 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 TER and increased paracellular permeability, but was not significantly altered after salmeterol pre-incubation. These results demonstrate that salmeterol may contribute to the protection of the airway epithelium barrier against bacterial virulence factors.




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