Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells

被引:108
作者
Schogler, Aline [1 ,2 ,3 ]
Kopf, Brigitte S. [1 ,2 ]
Edwards, Michael R. [4 ,5 ]
Johnston, Sebastian L. [4 ,5 ]
Casaultal, Carmen [1 ]
Kieninger, Elisabeth [1 ]
Jung, Andreas [6 ]
Moeller, Alexander [6 ]
Geiser, Thomas [2 ,7 ]
Regamey, Nicolas [1 ,2 ]
Alves, Marco P. [1 ,2 ]
机构
[1] Univ Childrens Hosp, Div Paediat Resp Med, Bern, Switzerland
[2] Univ Bern, Dept Clin Res, Bern, Switzerland
[3] Univ Bern, Grad Sch Cellular & Biomed Sci, Bern, Switzerland
[4] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Ctr Resp, London, England
[5] Univ London Imperial Coll Sci Technol & Med, Airway Dis Infect Sect, MRC, Asthma UK Ctr Allerg Mech Asthma, London, England
[6] Univ Childrens Hosp, Div Resp Med, Zurich, Switzerland
[7] Univ Hosp Bern, Dept Pulm Med, CH-3010 Bern, Switzerland
关键词
INHIBITS RHINOVIRUS INFECTION; RESPIRATORY VIRUSES; GENE-EXPRESSION; YOUNG-CHILDREN; INTERFERON; IMPACT; ALPHA; BLOOD;
D O I
10.1183/09031936.00102014
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Virus-associated pulmonary exacerbations, often associated with rhinoviruses (RVs), contribute to cystic fibrosis (CF) morbidity. Currently, there are only a few therapeutic options to treat virus-induced CF pulmonary exacerbations. The macrolide antibiotic azithromycin has antiviral properties in human bronchial epithelial cells. We investigated the potential of azithromycin to induce antiviral mechanisms in CF bronchial epithelial cells. Primary bronchial epithelial cells from CF and control children were infected with RV after azithromycin pre-treatment. Viral RNA, interferon (IFN), IFN-stimulated gene and pattern recognition receptor expression were measured by real-time quantitative PCR. Live virus shedding was assessed by assaying the 50% tissue culture infective dose. Pro-inflammatory cytokine and IFN-beta production were evaluated by ELISA. Cell death was investigated by flow cytometry. RV replication was increased in CF compared with control cells. Azithromycin reduced RV replication seven-fold in CF cells without inducing cell death. Furthermore, azithromycin increased RV-induced pattern recognition receptor, IFN and IFN-stimulated gene mRNA levels. While stimulating antiviral responses, azithromycin did not prevent virus-induced pro-inflammatory responses. Azithromycin pre-treatment reduces RV replication in CF bronchial epithelial cells, possibly through the amplification of the antiviral response mediated by the IFN pathway. Clinical studies are needed to elucidate the potential of azithromycin in the management and prevention of RV-induced CF pulmonary exacerbations.
引用
收藏
页码:428 / 439
页数:12
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