Effect of a cysteinyl leukotriene receptor antagonist on experimental emphysema and asthma combined with emphysema

Genyo Ikeda, Nobuaki Miyahara, Hikari Koga, Yasuko Fuchimoto, Koichi Waseda, Etsuko Kurimoto, Akihiko Taniguchi, Yasushi Tanimoto, Mikio Kataoka, Mitsune Tanimoto, Arihiko Kanehiro

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The incidence of overlapping bronchial asthma and chronic obstructive pulmonary disease has increased in recent years. Cysteinyl leukotrienes (CysLTs) play an important role in asthma, and the type 1 CysLT receptor (CysLT 1R) is expressed by many inflammatory cells. We evaluated the effect of montelukast, a CysLT1R antagonist, on mouse models of asthma, porcine pancreatic elastase (PPE)-induced emphysema, and asthma combined with emphysema. Mice were sensitized with ovalbumin (OVA) on Days 0 and 14 and subsequently challenged with OVA on Days 28, 29, and 30. Pulmonary emphysema was induced by intratracheal instillation of PPE on Day 25. Mice were treated subcutaneously with montelukast or vehicle from Day 25 to Day 31. Airway hyperresponsiveness (AHR), static compliance; the number of inflammatory cells, the levels of cytokines, chemokines, LTs, and perforin in the bronchoalveolar lavage fluid, and the quantitative morphometry of lung sections were analyzed on Day 32. Treatment with montelukast significantly attenuated the AHR and eosinophilic airway inflammation in OVA-sensitized and OVA-challenged mice. Administration of montelukast significantly reduced the AHR, static compliance, and neutrophilic airway inflammation, while attenuating emphysematous lung changes, in PPE-treated mice. In PPE-treated mice subjected to allergen sensitization and challenges, montelukast significantly suppressed the AHR, static compliance, and eosinophilic and neutrophilic airway inflammation in addition to the development of experimentally induced emphysema in the lungs. Our data suggest that CysLT1R antagonists may be effective in ameliorating the consequences of PPE-induced lung damage and the changes that follow allergen sensitization and challenges.

Original languageEnglish
Pages (from-to)18-29
Number of pages12
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume50
Issue number1
DOIs
Publication statusPublished - Jan 2014

Fingerprint

montelukast
Leukotriene Antagonists
Emphysema
Pancreatic Elastase
Asthma
Ovalbumin
Swine
Compliance
Lung
Inflammation
Allergens
Perforin
Pulmonary Emphysema
Bronchoalveolar Lavage Fluid
Pulmonary diseases
Chemokines
Chronic Obstructive Pulmonary Disease
leukotriene D4 receptor
Cell Count
Cytokines

Keywords

  • Asthma
  • Chronic obstructive pulmonary disease
  • Cysteinyl leukotriene
  • Cysteinyl leukotriene receptor
  • Overlap of asthma and chronic obstructive pulmonary disease

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Effect of a cysteinyl leukotriene receptor antagonist on experimental emphysema and asthma combined with emphysema. / Ikeda, Genyo; Miyahara, Nobuaki; Koga, Hikari; Fuchimoto, Yasuko; Waseda, Koichi; Kurimoto, Etsuko; Taniguchi, Akihiko; Tanimoto, Yasushi; Kataoka, Mikio; Tanimoto, Mitsune; Kanehiro, Arihiko.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 50, No. 1, 01.2014, p. 18-29.

Research output: Contribution to journalArticle

Ikeda, Genyo ; Miyahara, Nobuaki ; Koga, Hikari ; Fuchimoto, Yasuko ; Waseda, Koichi ; Kurimoto, Etsuko ; Taniguchi, Akihiko ; Tanimoto, Yasushi ; Kataoka, Mikio ; Tanimoto, Mitsune ; Kanehiro, Arihiko. / Effect of a cysteinyl leukotriene receptor antagonist on experimental emphysema and asthma combined with emphysema. In: American Journal of Respiratory Cell and Molecular Biology. 2014 ; Vol. 50, No. 1. pp. 18-29.
@article{9bcba7d6ac404fa0821f4b0af705a5e5,
title = "Effect of a cysteinyl leukotriene receptor antagonist on experimental emphysema and asthma combined with emphysema",
abstract = "The incidence of overlapping bronchial asthma and chronic obstructive pulmonary disease has increased in recent years. Cysteinyl leukotrienes (CysLTs) play an important role in asthma, and the type 1 CysLT receptor (CysLT 1R) is expressed by many inflammatory cells. We evaluated the effect of montelukast, a CysLT1R antagonist, on mouse models of asthma, porcine pancreatic elastase (PPE)-induced emphysema, and asthma combined with emphysema. Mice were sensitized with ovalbumin (OVA) on Days 0 and 14 and subsequently challenged with OVA on Days 28, 29, and 30. Pulmonary emphysema was induced by intratracheal instillation of PPE on Day 25. Mice were treated subcutaneously with montelukast or vehicle from Day 25 to Day 31. Airway hyperresponsiveness (AHR), static compliance; the number of inflammatory cells, the levels of cytokines, chemokines, LTs, and perforin in the bronchoalveolar lavage fluid, and the quantitative morphometry of lung sections were analyzed on Day 32. Treatment with montelukast significantly attenuated the AHR and eosinophilic airway inflammation in OVA-sensitized and OVA-challenged mice. Administration of montelukast significantly reduced the AHR, static compliance, and neutrophilic airway inflammation, while attenuating emphysematous lung changes, in PPE-treated mice. In PPE-treated mice subjected to allergen sensitization and challenges, montelukast significantly suppressed the AHR, static compliance, and eosinophilic and neutrophilic airway inflammation in addition to the development of experimentally induced emphysema in the lungs. Our data suggest that CysLT1R antagonists may be effective in ameliorating the consequences of PPE-induced lung damage and the changes that follow allergen sensitization and challenges.",
keywords = "Asthma, Chronic obstructive pulmonary disease, Cysteinyl leukotriene, Cysteinyl leukotriene receptor, Overlap of asthma and chronic obstructive pulmonary disease",
author = "Genyo Ikeda and Nobuaki Miyahara and Hikari Koga and Yasuko Fuchimoto and Koichi Waseda and Etsuko Kurimoto and Akihiko Taniguchi and Yasushi Tanimoto and Mikio Kataoka and Mitsune Tanimoto and Arihiko Kanehiro",
year = "2014",
month = "1",
doi = "10.1165/rcmb.2012-0418OC",
language = "English",
volume = "50",
pages = "18--29",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "1",

}

TY - JOUR

T1 - Effect of a cysteinyl leukotriene receptor antagonist on experimental emphysema and asthma combined with emphysema

AU - Ikeda, Genyo

AU - Miyahara, Nobuaki

AU - Koga, Hikari

AU - Fuchimoto, Yasuko

AU - Waseda, Koichi

AU - Kurimoto, Etsuko

AU - Taniguchi, Akihiko

AU - Tanimoto, Yasushi

AU - Kataoka, Mikio

AU - Tanimoto, Mitsune

AU - Kanehiro, Arihiko

PY - 2014/1

Y1 - 2014/1

N2 - The incidence of overlapping bronchial asthma and chronic obstructive pulmonary disease has increased in recent years. Cysteinyl leukotrienes (CysLTs) play an important role in asthma, and the type 1 CysLT receptor (CysLT 1R) is expressed by many inflammatory cells. We evaluated the effect of montelukast, a CysLT1R antagonist, on mouse models of asthma, porcine pancreatic elastase (PPE)-induced emphysema, and asthma combined with emphysema. Mice were sensitized with ovalbumin (OVA) on Days 0 and 14 and subsequently challenged with OVA on Days 28, 29, and 30. Pulmonary emphysema was induced by intratracheal instillation of PPE on Day 25. Mice were treated subcutaneously with montelukast or vehicle from Day 25 to Day 31. Airway hyperresponsiveness (AHR), static compliance; the number of inflammatory cells, the levels of cytokines, chemokines, LTs, and perforin in the bronchoalveolar lavage fluid, and the quantitative morphometry of lung sections were analyzed on Day 32. Treatment with montelukast significantly attenuated the AHR and eosinophilic airway inflammation in OVA-sensitized and OVA-challenged mice. Administration of montelukast significantly reduced the AHR, static compliance, and neutrophilic airway inflammation, while attenuating emphysematous lung changes, in PPE-treated mice. In PPE-treated mice subjected to allergen sensitization and challenges, montelukast significantly suppressed the AHR, static compliance, and eosinophilic and neutrophilic airway inflammation in addition to the development of experimentally induced emphysema in the lungs. Our data suggest that CysLT1R antagonists may be effective in ameliorating the consequences of PPE-induced lung damage and the changes that follow allergen sensitization and challenges.

AB - The incidence of overlapping bronchial asthma and chronic obstructive pulmonary disease has increased in recent years. Cysteinyl leukotrienes (CysLTs) play an important role in asthma, and the type 1 CysLT receptor (CysLT 1R) is expressed by many inflammatory cells. We evaluated the effect of montelukast, a CysLT1R antagonist, on mouse models of asthma, porcine pancreatic elastase (PPE)-induced emphysema, and asthma combined with emphysema. Mice were sensitized with ovalbumin (OVA) on Days 0 and 14 and subsequently challenged with OVA on Days 28, 29, and 30. Pulmonary emphysema was induced by intratracheal instillation of PPE on Day 25. Mice were treated subcutaneously with montelukast or vehicle from Day 25 to Day 31. Airway hyperresponsiveness (AHR), static compliance; the number of inflammatory cells, the levels of cytokines, chemokines, LTs, and perforin in the bronchoalveolar lavage fluid, and the quantitative morphometry of lung sections were analyzed on Day 32. Treatment with montelukast significantly attenuated the AHR and eosinophilic airway inflammation in OVA-sensitized and OVA-challenged mice. Administration of montelukast significantly reduced the AHR, static compliance, and neutrophilic airway inflammation, while attenuating emphysematous lung changes, in PPE-treated mice. In PPE-treated mice subjected to allergen sensitization and challenges, montelukast significantly suppressed the AHR, static compliance, and eosinophilic and neutrophilic airway inflammation in addition to the development of experimentally induced emphysema in the lungs. Our data suggest that CysLT1R antagonists may be effective in ameliorating the consequences of PPE-induced lung damage and the changes that follow allergen sensitization and challenges.

KW - Asthma

KW - Chronic obstructive pulmonary disease

KW - Cysteinyl leukotriene

KW - Cysteinyl leukotriene receptor

KW - Overlap of asthma and chronic obstructive pulmonary disease

UR - http://www.scopus.com/inward/record.url?scp=84891783155&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891783155&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2012-0418OC

DO - 10.1165/rcmb.2012-0418OC

M3 - Article

C2 - 23937413

AN - SCOPUS:84891783155

VL - 50

SP - 18

EP - 29

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 1

ER -