論文

査読有り
2012年8月

A Novel Prostacyclin Agonist Protects against Airway Hyperresponsiveness and Remodeling in Mice

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
  • Cristiane Yamabayashi
  • Toshiyuki Koya
  • Hiroshi Kagamu
  • Hidenori Kawakami
  • Yosuke Kimura
  • Toshiki Furukawa
  • Takuro Sakagami
  • Takashi Hasegawa
  • Yoshiki Sakai
  • Kunio Matsumoto
  • Mizuho Nakayama
  • Erwin W. Gelfand
  • Eiichi Suzuki
  • Ichiei Narita
  • 全て表示

47
2
開始ページ
170
終了ページ
177
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1165/rcmb.2011-0350OC
出版者・発行元
AMER THORACIC SOC

Airway remodeling in bronchial asthma results from chronic, persistent airway inflammation. The effects of the reversal of airway remodeling by drug interventions remain to be elucidated. We investigated the effects of ONO-1301, a novel prostacyclin agonist with thromboxane inhibitory activity, on the prevention and reversibility of airway remodeling in an experimental chronic asthma model. Mice sensitized and challenged to ovalbumin (OVA) three times a week for 5 consecutive weeks were administered ONO-1301 or vehicle twice a day from the fourth week of OVA challenges. Twenty-four hours after the final OVA challenge, airway hyperresponsiveness (AHR) was assessed, and bronchoalveolar lavage was performed. Lung specimens were excised for staining to detect goblet-cell metaplasia, airway smooth muscle, and submucosal fibrosis. Mice administered ONO-1301 showed limited increases in AHR compared with mice administered the vehicle. The histological findings of airway remodeling were improved in ONO-1301-treated mice compared with vehicle-treated mice. Presumably, these therapeutic effects of ONO-1301 are attributable to the up-regulation of production of hepatocyte growth factor (HGF) in lung tissue, because the neutralization of HGF by antibodies prevented the effects of ONO-1301 on AHR and airway remodeling. Mice administered ONO-1301 showed similar levels of AHR and airway remodeling as mice administered montelukast, a cysteinyl-leukotriene-1 receptor antagonist, and lower levels were observed in mice administered dexamethasone. These data suggest that ONO-1301 exerts the effect of reversing airway remodeling, at least in part through an elevation of HGF in the lungs, and may be effective as an anti-remodeling drug in the treatment of asthma.

リンク情報
DOI
https://doi.org/10.1165/rcmb.2011-0350OC
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22403804
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000307365300005&DestApp=WOS_CPL
ID情報
  • DOI : 10.1165/rcmb.2011-0350OC
  • ISSN : 1044-1549
  • eISSN : 1535-4989
  • PubMed ID : 22403804
  • Web of Science ID : WOS:000307365300005

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