Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells.

Schögler, Aline; Kopf, BS; Edwards, MR; Johnston, SL; Casaulta Aebischer, Carmen; Kieninger, Elisabeth; Jung, A; Moeller, A; Geiser, Thomas; Regamey, Nicolas; Alves, Marco P (2015). Novel antiviral properties of azithromycin in cystic fibrosis airway epithelial cells. European respiratory journal, 45(2), pp. 428-439. European Respiratory Society 10.1183/09031936.00102014

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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-β 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pneumologie (Pädiatrie)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

UniBE Contributor:

Schögler, Aline; Casaulta Aebischer, Carmen; Kieninger, Elisabeth; Geiser, Thomas and Regamey, Nicolas

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0903-1936

Publisher:

European Respiratory Society

Language:

English

Submitter:

Rahel Holderegger

Date Deposited:

10 Mar 2015 08:54

Last Modified:

29 Oct 2015 10:59

Publisher DOI:

10.1183/09031936.00102014

PubMed ID:

25359346

BORIS DOI:

10.7892/boris.64362

URI:

https://boris.unibe.ch/id/eprint/64362

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