Novel effects of azithromycin on tight junction proteins in human airway epithelia
Novel effects of azithromycin on tight junction proteins in human airway epithelia
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DOI：
10.1128/aac.50.5.1805-1812.2006
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发表时间：
2006-05-01
影响因子：
4.9
通讯作者：
Baldursson, O
中科院分区：
文献类型：
--
作者：
Asgrimsson, V;Gudjonsson, T;Baldursson, O
大环内酯类抗生素阿奇霉素改善囊性纤维化或弥漫性泛细支气管炎患者的肺功能和预后，不依赖于细菌根除。抗炎作用已被牵连，但来自体内研究的数据很少，而且呼吸道表面液体中异常电解质含量与支气管感染之间的联系仍不确定。在本研究中，我们用阿奇霉素处理滤器支架上的人呼吸道上皮细胞，并监测跨上皮电阻值。我们发现阿奇霉素以剂量依赖的方式增加了呼吸道上皮细胞的跨上皮电阻。免疫细胞化学和Western blotting显示，加入阿奇霉素改变了蛋白质在细胞培养中的位置，并诱导紧密连接蛋白claudin-1和claudin-4、occludin和连接黏附分子-A的加工。这些效应是可逆的，当用青霉素或红霉素处理细胞时，没有看到任何影响。结果表明，阿奇霉素通过改变紧密连接蛋白的加工而增加人呼吸道上皮细胞的跨上皮电阻。这些结果是新的，可能有助于解释阿奇霉素对囊性纤维化、弥漫性泛细支气管炎和社区获得性肺炎患者的益处。
The macrolide antibiotic azithromycin improves lung function and prognosis among patients with cystic fibrosis or diffuse panbronchiolitis, independently of bacterial eradication. Anti-inflammatory effects have been implicated, but data from in vivo studies are scarce, and the link between abnormal electrolyte content in airway surface liquid and bronchial infections remains uncertain. In the present study, we treated human airway epithelia on filter supports with azithromycin and monitored transepithelial electrical resistance. We found that azithromycin increased transepithelial electrical resistance of airway epithelia in a dose-dependent manner. Immunocytochemistry and Western blotting showed that addition of azithromycin changed the locations of proteins in cell cultures and induced processing of the tight junction proteins claudin-1 and claudin-4, occludin, and junctional adhesion molecule-A. These effects were reversible, and no effect was seen when cells were treated with penicillin or erythromycin. The data indicate that azithromycin increases the transepithelial electrical resistance of human airway epithelia by changing the processing of tight junction proteins. The results are novel and may help explain the beneficial effects of azithromycin in patients with cystic fibrosis, diffuse panbronchiolitis, and community-acquired pneumonia.