Montelukast suppresses EMT @ bronchial epithelial cells by eosinophils

Highlights

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Inhibition of EMT by montelukast was evaluated.

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EMT was assessed using a co-culture system of epithelial cells and eosinophils.

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Montelukast inhibited EMT induced in the co-culture system.

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Montelukast decreased TGF-β1 production and Smad3 phosphorylation.

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Eosinophils significantly enhanced CysLTs production but montelukast inhibited it.

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Abstract

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.

Keywords

• Airway remodeling;
• Asthma;
• Cysteinyl leukotrienes;
• Epithelial to mesenchymal transition;
• Eosinophils;
• Montelukast

Corresponding author. Address: Department of Immunology, Mie University Graduate School of Medicine, Edobashi 2-174, 514-8507 Tsu-city, Mie, Japan. Fax: +81 59 231 5225.