INSERM, U903, Reims F-51092, France.
Respir Res. 2010 Jan 20;11(1):6. doi: 10.1186/1465-9921-11-6.
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.
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.
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.
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.
金黄色葡萄球菌释放的毒力因子（VF）可能会损害气道细胞的先天保护功能。本研究旨在确定长效β2 肾上腺素能受体激动剂（沙美特罗羟萘酸酯，Sal）与皮质类固醇（丙酸氟替卡松，FP）联合应用是否能调节气道腺细胞暴露于金黄色葡萄球菌上清液后的离子含量和细胞因子表达。
用人气道腺细胞系孵育金黄色葡萄球菌上清液 1 小时，然后用 Sal/FP 联合处理 4 小时。通过免疫荧光法分析肌动蛋白和 CFTR 蛋白的表达。视频显微镜用于评估氯离子分泌，X 射线微分析用于测量细胞内离子和水含量。通过 RT-PCR 和 ELISA 评估促炎细胞因子的表达。
当细胞与金黄色葡萄球菌上清液孵育，然后与 Sal/FP 孵育时，CFTR 的细胞定位为顶端，而单独与金黄色葡萄球菌上清液孵育时为细胞质定位。气道上皮细胞与金黄色葡萄球菌上清液孵育可使氯离子流出减少 66%，而 Sal/FP 处理可完全恢复氯离子流出。我们还观察到，Sal/FP 处理诱导气道腺细胞内分泌颗粒中离子（Cl 和 S）和水含量的恢复，并降低细菌上清液依赖性促炎细胞因子 IL8 和 TNFalpha 的增加。
我们的结果表明，在细菌感染后用皮质类固醇和长效β2 肾上腺素能受体激动剂联合治疗可恢复气道腺细胞功能。在肺部感染期间由于离子转运异常而引起的异常粘液可能受益于β2 肾上腺素能受体激动剂和糖皮质激素的联合治疗。
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