Long acting beta2-agonist and corticosteroid restore airway glandular cell function altered by bacterial supernatant.
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.
Zahm
Jean-Marie
JM
INSERM, U903, Reims F-51092, France. jm.zahm@univ-reims.fr
Delavoie
Franck
F
Toumi
Férial
F
Nawrocki-Raby
Béatrice
B
Kileztky
Claire
C
Michel
Jean
J
Balossier
Gérard
G
Johnson
Malcolm
M
Coraux
Christelle
C
Birembaut
Philippe
P
D058672:Adrenergic beta-2 Receptor Antagonists; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D006801:Humans; D020545:Respiratory Mucosa / Q000187:drug effects / Q000382:microbiology* / Q000502:physiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology*
D058672:Adrenergic beta-2 Receptor Antagonists; D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D000420:Albuterol