Opin vísindi

Azithromycin induces epidermal differentiation and multivesicular bodies in airway epithelia

Azithromycin induces epidermal differentiation and multivesicular bodies in airway epithelia

Title: Azithromycin induces epidermal differentiation and multivesicular bodies in airway epithelia
Author: Arason, Ari Jon   orcid.org/0000-0003-0252-7992
Jóelsson, Jón Pétur
Valdimarsdóttir, Bryndís
Sigurdsson, Snaevar   orcid.org/0000-0003-4860-6311
Guðjónsson, Alexander
Halldorsson, Skarphedinn   orcid.org/0000-0003-4337-9252
Jóhannsson, Freyr   orcid.org/0000-0001-6460-2463
Rolfsson, Óttar   orcid.org/0000-0003-4258-6057
Lehmann, Fredrik
Ingthorsson, Saevar   orcid.org/0000-0001-8480-9680
... 7 more authors Show all authors
Date: 2019-06-24
Language: English
Scope: 129
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Lífvísindasetur (HÍ)
Biomedical Center (UI)
Rannsóknarsetur í kerfislíffræði (HÍ)
Center for Systems Biology (UI)
Læknadeild (HÍ)
Faculty of Medicine (UI)
Líf- og umhverfisvísindadeild (HÍ)
Faculty of Life and Environmental Sciences (UI)
Series: Respiratory Research;20(1)
ISSN: 1465-993X
DOI: 10.1186/s12931-019-1101-3
Subject: Air-liquid interface; Airway; Azithromycin; Epidermal differentiation; Epithelia; Gene expression; Genarannsóknir; Öndunarfæri; Öndunarfærasjúkdómar
URI: https://hdl.handle.net/20.500.11815/1688

Show full item record


Arason, A.J., Joelsson, J.P., Valdimarsdottir, B. et al. Azithromycin induces epidermal differentiation and multivesicular bodies in airway epithelia. Respiratory research 20, 129 (2019). https://doi.org/10.1186/s12931-019-1101-3


BACKGROUND: Azithromycin (Azm) is a macrolide recognized for its disease-modifying effects and reduction in exacerbation of chronic airway diseases. It is not clear whether the beneficial effects of Azm are due to its anti-microbial activity or other pharmacological actions. We have shown that Azm affects the integrity of the bronchial epithelial barrier measured by increased transepithelial electrical resistance. To better understand these effects of Azm on bronchial epithelia we have investigated global changes in gene expression. METHODS: VA10 bronchial epithelial cells were treated with Azm and cultivated in air-liquid interface conditions for up to 22 days. RNA was isolated at days 4, 10 and 22 and analyzed using high-throughput RNA sequencing. qPCR and immunostaining were used to confirm key findings from bioinformatic analyses. Detailed assessment of cellular changes was done using microscopy, followed by characterization of the lipidomic profiles of the multivesicular bodies present. RESULTS: Bioinformatic analysis revealed that after 10 days of treatment genes encoding effectors of sterol and cholesterol metabolism were prominent. Interestingly, expression of genes associated with epidermal barrier differentiation, KRT1, CRNN, SPINK5 and DSG1, increased significantly at day 22. Together with immunostaining, these results suggest an epidermal differentiation pattern. We also found that Azm induced the formation of multivesicular and lamellar bodies in two different airway epithelial cell lines. Lipidomic analysis revealed that Azm was entrapped in multivesicular bodies linked to different types of lipids, most notably palmitate and stearate. Furthermore, targeted analysis of lipid species showed accumulation of phosphatidylcholines, as well as ceramide derivatives. CONCLUSIONS: Taken together, we demonstrate how Azm might confer its barrier enhancing effects, via activation of epidermal characteristics and changes to intracellular lipid dynamics. These effects of Azm could explain the unexpected clinical benefit observed during Azm-treatment of patients with various lung diseases affecting barrier function.


Publisher's version (útgefin grein)


Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Files in this item

This item appears in the following Collection(s)