Long acting β2-agonist and corticosteroid restore airway glandular cell function altered by bacterial supernatant.

Abstract : BACKGROUND: Staphylococcus aureus releases virulence factors (VF) that may impair the innate protective functions of airway cells. The aim of this study was to determine whether a long-acting beta2 adrenergic receptor agonist (salmeterol hydroxynaphthoate, Sal) combined with a corticosteroid (fluticasone propionate, FP) was able to regulate ion content and cytokine expression by airway glandular cells after exposure to S. aureus supernatant. METHODS: A human airway glandular cell line was incubated with S. aureus supernatant for 1 h and then treated with the combination Sal/FP for 4 h. The expression of actin and CFTR proteins was analyzed by immunofluorescence. Videomicroscopy was used to evaluate chloride secretion and X-ray microanalysis to measure the intracellular ion and water content. The pro-inflammatory cytokine expression was assessed by RT-PCR and ELISA. RESULTS: When the cells were incubated with S. aureus supernatant and then with Sal/FP, the cellular localisation of CFTR was apical compared to the cytoplasmic localisation in cells incubated with S. aureus supernatant alone. The incubation of airway epithelial cells with S. aureus supernatant reduced by 66% the chloride efflux that was fully restored by Sal/FP treatment. We also observed that Sal/FP treatment induced the restoration of ion (Cl and S) and water content within the intracellular secretory granules of airway glandular cells and reduced the bacterial supernatant-dependent increase of pro-inflammatory cytokines IL8 and TNFalpha. CONCLUSIONS: Our results demonstrate that treatment with the combination of a corticosteroid and a long-acting beta2 adrenergic receptor agonist after bacterial infection restores the airway glandular cell function. Abnormal mucus induced by defective ion transport during pulmonary infection could benefit from treatment with a combination of beta2 adrenergic receptor agonist and glucocorticoid.
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Respiratory Research, BioMed Central, 2010, 11 (1), pp.6. 〈10.1186/1465-9921-11-6〉
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Jean-Marie Zahm, Franck Delavoie, Férial Toumi, Béatrice Nawrocki-Raby, Claire Kileztky, et al.. Long acting β2-agonist and corticosteroid restore airway glandular cell function altered by bacterial supernatant.. Respiratory Research, BioMed Central, 2010, 11 (1), pp.6. 〈10.1186/1465-9921-11-6〉. 〈inserm-00663538〉

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