ArticleRespiratory research2019
Azithromycin induces epidermal differentiation and multivesicular bodies in airway epithelia.
Article in Respiratory research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 38 citations in OpenAlex.
- In Vitro and In Vivo Efficacy of Epithelial Barrier-Promoting Barriolides as Potential Therapy for Ulcerative Colitis.Biomedicines · 2026Article
- The Non-Antibacterial Effects of Azithromycin and Other Macrolides on the Bronchial Epithelial Barrier and Cellular Differentiation.International journal of molecular sciences · 2025Article
- Azithromycin mitigates human rhinovirus impact on barrier integrity and function in non-diseased airway epithelium.Frontiers in cell and developmental biology · 2025Article
- Azithromycin ameliorated cigarette smoke-induced airway epithelial barrier dysfunction by activating Nrf2/GCL/GSH signaling pathway.Respiratory research · 2023Article
- Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries.Antioxidants (Basel, Switzerland) · 2023Review
- Modulation of innate immunity in airway epithelium for host-directed therapy.Frontiers in immunology · 2023Review
- Impact of covid-19 on mental health and aging.Saudi journal of biological sciences · 2021Review
- Article
- Liquid and Solid Self-Emulsifying Drug Delivery Systems (SEDDs) as Carriers for the Oral Delivery of Azithromycin: Optimization, In Vitro Characterization and Stability Assessment.Pharmaceutics · 2020Article
- Azithromycin ameliorates sulfur dioxide-induced airway epithelial damage and inflammatory responses.Respiratory research · 2020Article
- Mechanism of azithromycin in airway diseases.The Journal of international medical research · 2020Review
- Host Directed Therapy Against Infection by Boosting Innate Immunity.Frontiers in immunology · 2020Review
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundAzithromycin (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.
methodsVA10 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.
resultsBioinformatic 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.
conclusionsTaken 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.
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