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Downregulation by a long-acting beta2-adrenergic receptor agonist and corticosteroid of Staphylococcus aureus-induced airway epithelial inflammatory mediator production.

Fragaki K, Kileztky C, Trentesaux C, Zahm JM, Bajolet O, Johnson M, Puchelle E

INSERM UMRS 514, IFR 53Centre Hospitalier Universitaire Maison Blanche, 45, rue Cognacq Jay, 51092 Reims Cedex, France.

Although Staphylococcus aureus is a major cause of pulmonary infection, the role played by this bacterium in the induction of inflammation of human airway epithelial cells (HAEC) is poorly understood. In this study, we investigated the inflammatory response of HAEC to S. aureus soluble virulence factors and demonstrate that the combination of a long-acting beta2-adrenergic receptor agonist (salmeterol) with a glucocorticoid (fluticasone propionate) has an anti-inflammatory effect on HAEC. First, we demonstrate increased expression at both the mRNA and protein levels of interleukin (IL)-8, IL-6, and tumor necrosis factor (TNF)-alpha following incubation of HAEC in the presence of S. aureus soluble virulence factors and the increase of 1) the free nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) activities and 2) the phosphorylated (P-) extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2), the P-c-Jun NH2-terminal kinase (JNK), and the P-isoform-alpha of the NF-kappaB inhibitor (IkappaB alpha). Next, when HAEC were preincubated with the combination of salmeterol and fluticasone propionate, the inflammatory response of HAEC was markedly attenuated in that levels of IL-8, IL-6, TNF-alpha, NF-kappaB, AP-1, P-ERK1/ERK2, P-JNK, and P-IkappaB alpha decreased significantly. These data emphasize the deleterious effect of S. aureus soluble virulence factors and suggest that the combination of a beta2-adrenergic receptor agonist with a glucocorticoid may attenuate the associated airway epithelial inflammation.

Published 8 June 2006 in Am J Physiol Lung Cell Mol Physiol, 291(1): L11-8.
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Volume 1 (2004)
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Staphylococcus Books

Staphylococcus aureus - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Staphylococcus aureus - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References