Downregulation by a long-acting β2-adrenergic receptor agonist and corticosteroid of Staphylococcus aureus-induced airway epithelial inflammatory mediator production

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 beta(2)-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-kappa B ( NF-kappa B) 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-kappa B inhibitor ( I kappa B 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-kappa B, AP-1, P-ERK1/ERK2, P-JNK, and P-I kappa B alpha decreased significantly. These data emphasize the deleterious effect of S. aureus soluble virulence factors and suggest that the combination of a beta(2)-adrenergic receptor agonist with a glucocorticoid may attenuate the associated airway epithelial inflammation.