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Contextual role of azithromycin as an inhibitor of epithelial to mesenchymal transition in respiratory epithelium

Svandís Davíðsdóttir, Árni Ásbjarnarson, Felicity Herbert, Bryndís Valdimarsdóttir, Þórarinn Guðjónsson

Introduction. Epithelial to mesenchymal transition (EMT) is seen during embryonic development and in various diseases, including chronic respiratory diseases. EMT is governed by various transcription and growth factors, for example TGFβ1, which activates pathways that ultimately result in phenotypic changes. We have shown that Azithromycin (AZM), a commonly prescribed antibiotic, maintains epithelial integrity in bronchial epithelial cells. The aim of this study was to analyse if and how AZM may inhibit EMT in vitro, both in a 2D and 3D context.
Material and Methods. The bronchial and alveolar epithelial cell lines VA10 and A549 were cultured in monolayer, air-liquid interface (ALI) and in 3D matrix. Phenotypic changes were evaluated by RT-PCR, Western blot, immunostaining and RNA seq. EMT was induced via exposure to 10 ng/ml TGFβ1 to AZM pre-treated and non-treated cells.
Results. In monolayer, AZM is not able to restore TGFβ1-induced downregulation of E-cadherin or EpCAM but inhibits the expression of the mesenchymal markers vimentin and N-cadherin. The inhibition of EMT is more pronounced in ALI culture. RNA seq. analysis of ALI culture reveals that AZM affects the TGFβ1 and Wnt pathways. Results from 3D culture are still pending.
Conclusion. We demonstrate that AZM may be an efficient inhibitor of EMT in lung epithelial cells in vitro. However, this may depend on the context of the cellular assay used. Further studies are needed to evaluate the potential of AZM as a drug against EMT in respiratory diseases.


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