Azithromycin Influences Airway Remodeling in Asthma Via the PI3K/Akt/MTOR/HIF-1α/VEGF Pathway

Asthma is a respiratory disease that affects people of all walks of life, and is a hotspot of continuous research, with significant manpower and resources invested in its study. Airway remodeling is an important associated pathological change, and a mark of the irreversible damage produced by asthma. It involves compositional and functional changes in the cells of the airway walls, leading to reversible structural changes, and complicating treatment. Airway remodeling is mediated by different inflammatory pathways which have been targeted for treatment, with good results. However, given its complexity, systematic study of the pathogenesis of airway remodeling is still needed, and additional targeted therapies are necessary. Macrolide drugs, such as erythromycin, azithromycin, and clarithromycin, have antibacterial effects and also influence the cytokine secretion of macrophages and T-lymphocytes. They have direct effects on a variety of cytokines, inhibiting inflammation and reducing airway reactivity. In this study, we investigated the protective effect of azithromycin on airway remodeling through the phosphoinositol-3 kinase/Akt/mechanistic target of rapamycin kinase/hypoxia-inducible factor 1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. We observed that a long course of azithromycin could significantly reduce airway reactivity and ovalbulmin-induced pathological alterations in asthmatic mice. Gene expression analysis confirmed that HIF-1α and VEGF were significantly down-regulated following a long course of azithromycin administration.