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.
Institute for Clinical Research, Mie National Hospital, Japan; Department of Immunology, Mie University Graduate School of Medicine, Japan.
Koa
K
Hosoki
Institute for Clinical Research, Mie National Hospital, Japan.
Keigo
K
Kainuma
Department of Immunology, Mie University Graduate School of Medicine, Japan.
Masaaki
M
Toda
Department of Immunology, Mie University Graduate School of Medicine, Japan; Iwade Research Institute of Mycology, Japan.
Etsuko
E
Harada
Department of Immunology, Mie University Graduate School of Medicine, Japan.
Ayshwarya-Lakshmi
AL
Chelakkot-Govindalayathila
Department of Immunology, Mie University Graduate School of Medicine, Japan.
Ziaurahman
Z
Roeen
Department of Immunology, Mie University Graduate School of Medicine, Japan.
Mizuho
M
Nagao
Department of Immunology, Mie University Graduate School of Medicine, Japan.
Corina N
CN
D'Alessandro-Gabazza
Institute for Clinical Research, Mie National Hospital, Japan.
Takao
T
Fujisawa
Institute for Clinical Research, Mie National Hospital, Japan. Electronic address: gabazza@clin.medic.mie-u.ac.jp.
Esteban C
EC
Gabazza
D000085:Acetates / Q000494:pharmacology*; D056151:Airway Remodeling / Q000187:drug effects*; D001249:Asthma / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D024042:Collagen Type I / Q000378:metabolism; D003521:Cyclopropanes; D003545:Cysteine / Q000037:antagonists & inhibitors; D004804:Eosinophils / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D015289:Leukotrienes; D010766:Phosphorylation; D011804:Quinolines / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects*; D051900:Smad3 Protein / Q000378:metabolism; D013440:Sulfides; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D000085:Acetates; D024042:Collagen Type I; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011804:Quinolines; D051900:Smad3 Protein; D013440:Sulfides; D053773:Transforming Growth Factor beta1; D014746:Vimentin; C112381:cysteinyl-leukotriene; D003545:Cysteine; C093875:montelukast
Airway remodeling; Asthma; Cysteinyl leukotrienes; Eosinophils; Epithelial to mesenchymal transition; Montelukast