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Roflumilast Ameliorates Airway Hyperresponsiveness Caused by Diet-Induced Obesity in a Murine Model

Authors
 Hye Jung Park  ;  Jae-Hyun Lee  ;  Yoon Hee Park  ;  Heejae Han  ;  Da Woon Sim  ;  Kyung Hee Park  ;  Jung-Won Park 
Citation
 American Journal of Respiratory Cell and Molecular Biology, Vol.55(1) : 82-91, 2016 
Journal Title
 American Journal of Respiratory Cell and Molecular Biology 
Issue Date
2016
Abstract
Obese patients with asthma respond poorly to conventional asthma medications, resulting in severe symptoms and poor prognosis. Roflumilast, a phosphodiesterase-4 inhibitor that lowers the levels of various substances that are implicated in obese subjects with asthma, may be effective in the treatment of those subjects. We evaluated the potential of roflumilast as a novel therapeutic agent for obese subjects with asthma. We designed three models: diet-induced obesity (DIO); DIO with ovalbumin (OVA); and OVA. We fed C57BL/6J mice a high-fat diet for 3 months with or without OVA sensitization and challenge. Roflumilast or dexamethasone was administered orally three times at 2-day intervals in the last experimental week. Airway hyperresponsiveness resulting from DIO significantly improved in the roflumilast-treated group compared with the dexamethasone-treated groups. Although DIO did not affect the cell proliferation in bronchoalveolar lavage fluid, increased fibrosis was seen in the DIO group, which significantly improved from treatment with roflumilast. DIO-induced changes in adiponectin and leptin levels were improved by roflumilast, whereas dexamethasone aggravated them. mRNA levels and proteins of TNF-α, transforming growth factor-β, IL-1β, and IFN-γ increased in the DIO group and decreased with roflumilast. The reactive oxygen species levels were also increased in the DIO group and decreased by roflumilast. In the DIO plus OVA and OVA models, roflumilast improved Th1 and Th2 cell activation to a greater extent than dexamethasone. Roflumilast is significantly more effective than dexamethasone against airway hyperresponsiveness caused by DIO in the murine model. Roflumilast may represent a promising therapeutic agent for the treatment of obese patients with asthma.
Full Text
http://www.atsjournals.org/doi/abs/10.1165/rcmb.2015-0345OC
DOI
10.1165/rcmb.2015-0345OC
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
박경희(Park, Kyung Hee) ORCID logo https://orcid.org/0000-0003-3605-5364
박윤희(Park, Yoon Hee)
박중원(Park, Jung Won) ORCID logo https://orcid.org/0000-0003-0249-8749
박혜정(Park, Hye Jung) ORCID logo https://orcid.org/0000-0002-1862-1003
심다운(Sim, Da Woon)
이재현(Lee, Jae Hyun) ORCID logo https://orcid.org/0000-0002-0760-0071
한희재(Han, Heejae)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/155729
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