Oliynyk Igor, Varelogianni Georgia, Schalling Martin, Asplund Monika Stenkvist, Roomans Godfried M, Johannesson Marie
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Exp Lung Res. 2009 Apr;35(3):210-21. doi: 10.1080/01902140802534967.
It was investigated whether azithromycin (AZM) stimulates chloride (Cl-) efflux from cystic fibrosis (CF) and non-CF airway epithelial cells, possibly secondary to up-regulation of the multidrug resistance protein (MDR). CF and non-CF human airway epithelial cell lines (CFBE and 16HBE) were treated with 0.4, 4, and 40 microg/mL AZM for 4 days. Cl- efflux was explored in the presence or absence of specific inhibitors of CFTR and alternative Cl- channels. Six CF patients received AZM (500 mg daily) for 6 months. The percentage of predicted forced vital capacity (FVC%), forced expiratory volume (FEV1%), and the number of acute exacerbations were compared before and after treatment. Nasal biopsies were taken before and after treatment, and mRNA expression of MDR and CFTR was determined by in situ hybridization. A significant dose-dependent increase of Cl- efflux from CFBE cells (but not from 16HBE cells) was observed after AZM treatment. A CFTR inhibitor significantly reduced AZM-stimulated Cl- efflux from CFBE cells. A significant improvement in FEV1%, and fewer exacerbations were observed. AZM treatment did not affect mRNA expression of MDR and CFTR. The stimulation of Cl- efflux could be part of the explanation for the clinical improvement seen among the patients.
研究了阿奇霉素（AZM）是否刺激囊性纤维化（CF）和非CF气道上皮细胞的氯离子（Cl-）外流，这可能继发于多药耐药蛋白（MDR）的上调。CF和非CF人气道上皮细胞系（CFBE和16HBE）用0.4、4和40μg/mL的AZM处理4天。在存在或不存在CFTR和替代Cl-通道的特异性抑制剂的情况下探究Cl-外流。6例CF患者接受AZM（每日500mg）治疗6个月。比较治疗前后预测的用力肺活量（FVC%）、用力呼气量（FEV1%）的百分比以及急性加重的次数。在治疗前后进行鼻活检，并通过原位杂交测定MDR和CFTR的mRNA表达。AZM治疗后观察到CFBE细胞（而非16HBE细胞）的Cl-外流有显著的剂量依赖性增加。CFTR抑制剂显著降低了AZM刺激的CFBE细胞的Cl-外流。观察到FEV1%有显著改善，且急性加重次数减少。AZM治疗不影响MDR和CFTR的mRNA表达。Cl-外流的刺激可能是患者临床改善的部分原因。
