Azithromycin and Other Macrolides Improve Bronchial Barrier and Cellular Differentiation
Nikhil Prasad Fact checked by:Thailand Medical News Team Mar 06, 2025 7 hours, 48 minutes ago
Medical News: Scientists Explore the Non-Antibiotic Benefits of Macrolides
Researchers from the University of Iceland, EpiEndo Pharmaceuticals, and Landspitali University Hospital in Iceland have discovered that the antibiotic azithromycin offers significant benefits beyond its traditional use. Their study examined how macrolides, including azithromycin, affect the bronchial epithelial barrier and cellular differentiation, shedding light on their potential role in treating respiratory conditions.
Azithromycin and Other Macrolides Improve Bronchial Barrier and Cellular Differentiation
The respiratory epithelium serves as a protective barrier against harmful inhaled agents. When this barrier fails, it can lead to inflammation and exacerbations in diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis.
While macrolides are commonly used to treat infections, they also have secondary effects that may help strengthen this barrier. This
Medical News report highlights how azithromycin outperformed other macrolides in enhancing epithelial barrier function and cellular differentiation.
Study Methodology and Key Findings
The research team conducted their study using VA10 bronchial epithelial cells grown in an air-liquid interface model. The cells were exposed to macrolides - azithromycin, clarithromycin, erythromycin, roxithromycin, solithromycin, and tobramycin - over a period of 14 to 21 days. The study evaluated the effect of these antibiotics on the epithelial barrier by measuring transepithelial electrical resistance (TEER), paracellular permeability, and gene expression changes.
Findings revealed that azithromycin had the most significant impact on improving barrier function. TEER measurements showed that azithromycin-treated cells had the highest resistance levels, indicating reduced permeability and stronger cell-to-cell junctions. Clarithromycin and erythromycin also increased TEER values but to a lesser extent than azithromycin. Paracellular permeability assays confirmed that azithromycin-treated cultures had the lowest permeability, meaning fewer substances could pass between cells.
Histological analysis further demonstrated that azithromycin treatment resulted in increased epithelial cell layer thickness, a sign of enhanced cellular differentiation. This was accompanied by increased phospholipid retention and vesicle formation, which contribute to better barrier integrity. In contrast, roxithromycin and tobramycin had moderate effects, while solithromycin showed limited impact on epithelial differentiation.
Implications for Treating Respiratory Diseases
The study highlights the potential of azithromycin in improving lung health beyond its antibacterial properties. The enhanced bronchial epithelial barrier function observed with azithromycin treatment suggests that it could help patients with COPD and cystic fibrosis by reducing exacerbations and improving overall lung stability. By strengthening cell junctions and reducing permeability, the drug may lower the
likelihood of harmful substances penetrating the respiratory epithelium and triggering inflammation.
Another key finding was that azithromycin influenced the expression of genes associated with keratinocyte differentiation and epithelial integrity. This suggests that the drug may help maintain the structural integrity of the airway lining. Furthermore, azithromycin’s ability to retain phospholipids within epithelial cells may contribute to its protective effects, preventing barrier degradation commonly seen in chronic lung conditions.
Conclusion
This research provides compelling evidence that azithromycin can significantly enhance the bronchial epithelial barrier and promote cellular differentiation, offering potential therapeutic benefits beyond its antibacterial effects. The study suggests that azithromycin’s unique ability to increase TEER, reduce permeability, and influence key gene expressions makes it a promising candidate for improving respiratory health. Clarithromycin and erythromycin also demonstrated beneficial effects, though not as pronounced as azithromycin.
Future studies are needed to further explore the mechanisms behind azithromycin’s action and its long-term impact on respiratory diseases. Given the rising concerns about antibiotic resistance, researchers are also investigating non-antibiotic macrolides that could provide similar benefits without contributing to bacterial resistance.
The study findings were published in the peer-reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/26/5/2287
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