Montelukast suppresses epithelial to mesenchymal transition of bronchial epithelial cells induced by eosinophils.
Epithelial to mesenchymal transition (EMT) is a mechanism by which eosinophils can induce airway remodeling. Montelukast, an antagonist of the cysteinyl leukotriene receptor, can suppress airway remodeling in asthma. The purpose of this study was to evaluate whether montelukast can ameliorate airway remodeling by blocking EMT induced by eosinophils. EMT induced was assessed using a co-culture system of human bronchial epithelial cells and human eosinophils or the eosinophilic leukemia cell lines, Eol-1. Montelukast inhibited co-culture associated morphological changes of BEAS-2b cells, decreased the expression of vimentin and collagen I, and increased the expression of E-cadherin. Montelukast mitigated the rise of TGF-β1 production and Smad3 phosphorylation. Co-culture of human eosinophils with BEAS-2B cells significantly enhanced the production of CysLTs compared with BEAS-2B cells or eosinophils alone. The increase of CysLTs was abolished by montelukast pre-treatment. Montelukast had similar effects when co-culture system of Eol-1 and BEAS-2B was used. This study showed that montelukast suppresses eosinophils-induced EMT of airway epithelial cells. This finding may explain the mechanism of montelukast-mediated amelioration of airway remodeling in bronchial asthma.
['Hosoki|Koa|K|', 'Kainuma|Keigo|K|', 'Toda|Masaaki|M|', 'Harada|Etsuko|E|', 'Chelakkot-Govindalayathila|Ayshwarya-Lakshmi|AL|', 'Roeen|Ziaurahman|Z|', 'Nagao|Mizuho|M|', "D'Alessandro-Gabazza|Corina N|CN|", 'Fujisawa|Takao|T|', 'Gabazza|Esteban C|EC|']
D000085:Acetates D056151:Airway Remodeling D001249:Asthma D001980:Bronchi D045744:Cell Line, Tumor D018920:Coculture Techniques D024042:Collagen Type I D003521:Cyclopropanes D003545:Cysteine D004804:Eosinophils D058750:Epithelial-Mesenchymal Transition D006801:Humans D020024:Leukotriene Antagonists D015289:Leukotrienes D010766:Phosphorylation D011804:Quinolines D020545:Respiratory Mucosa D051900:Smad3 Protein D013440:Sulfides D053773:Transforming Growth Factor beta1 D014746:Vimentin
Montelukast Epithelial to mesenchymal transition Eosinophils Airway remodeling Cysteinyl leukotrienes Asthma