Clarithromycin attenuates airway epithelial-mesenchymal transition in ovalbumin-induced asthmatic mice through modulation of Kv1.3 channels and PI3K/Akt signaling

• Published in: International immunopharmacology 2024-09, Vol.139, p.112624, Article 112624
• Main Authors: Sun, Bingqing, Shen, Kunlu, Zhao, Ruiheng, Li, Yun, Lin, Jiangtao
• Format: Article
• Language: English
• Subjects: Airway Remodeling - drug effects; Animals; Asthma - chemically induced; Asthma - drug therapy; Asthma - metabolism; Asthma - pathology; Clarithromycin; Clarithromycin - pharmacology; Clarithromycin - therapeutic use; Disease Models, Animal; Epithelial Cells - drug effects; Epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - drug effects; Female; Ficusin - pharmacology; Ficusin - therapeutic use; Humans; Kv1.3 channel; Kv1.3 Potassium Channel - antagonists & inhibitors; Kv1.3 Potassium Channel - metabolism; Mice; Mice, Inbred BALB C; Ovalbumin - immunology; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt signalling; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112624

•Airway epithelial-mesenchymal transition (EMT) is the important pathological feature of airway remodeling in asthma.•The potential of clarithromycin to modify airway tissue damage at lower doses supports its use in chronic airway inflammatory diseases and indicates its perspectives on research.•Macrolides may be thus the potential strategy for the treatment of airway changes in asthma. Airway epithelial-mesenchymal transition (EMT) is the important pathological feature of airway remodeling in asthma. While macrolides are not commonly used to treat asthma, they have been shown to have protective effects on the airways, in which mechanisms are not yet fully understood. This study aims to investigate the impact of clarithromycin on airway EMT in asthma and its potential mechanism. The results revealed an increase in Kv1.3 expression in the airways of ovalbumin (OVA)-induced asthmatic mice, with symptoms and pathological changes being alleviated after treatment with the Kv1.3 inhibitor 5-(4-phenoxybutoxy)psoralen (PAP-1). Clarithromycin was found to attenuate airway epithelial-mesenchymal transition through the inhibition of Kv1.3 and PI3K/Akt signaling. Further experiments in vitro confirmed that PAP-1 could mitigate EMT by modulating the PI3K/Akt signaling in airway epithelial cells undergoing transformation into mesenchymal cells. These findings confirmed that clarithromycin might have a certain protective effect on asthma-related airway remodeling and represent a promising treatment strategy.