title: Effect of roflumilast on airway remodelling in a murine model of chronic asthma.
abstract: Airway remodelling is associated with irreversible, or partially reversible, airflow obstruction and ultimately unresponsiveness to asthma therapies such as corticosteroids. Roflumilast is a selective phosphodiesterase-4 inhibitor that has an anti-inflammatory effect in chronic obstructive pulmonary disease (COPD).
  
  
  
  The objective of this study was to study the effect of roflumilast on airway inflammation and remodelling in a murine model of chronic asthma.
  
  
  
  BALB/c mice sensitized to ovalbumin (OVA) were chronically exposed to intranasal OVA administration twice a week for additional 3 months. Roflumilast was administered orally during the intranasal OVA challenge. A lung fibroblast cell line was used in the proliferation assay.
  
  
  
  Compared with control mice, mice chronically exposed to OVA developed eosinophilic airway inflammation, airway hyper-responsiveness (AHR), and exhibited features of airway remodelling. Administration of roflumilast significantly inhibited airway inflammation and AHR. Roflumilast also significantly decreased goblet cell hyperplasia and pulmonary fibrosis, which are parameters of airway remodelling. The levels of interleukin (IL)-4, IL-5, and IL-13 in the bronchoalveolar lavage (BAL) fluids were significantly lower in the roflumilast group. In vitro, roflumilast significantly inhibited stem cell factor (SCF)-induced cell proliferation of fibroblasts. The SCF concentration and mRNA expression in a murine model also significantly decreased with roflumilast treatment.
  
  
  
  These results suggest that the administration of roflumilast regulates airway inflammation, AHR, and airway remodelling in a model of chronic asthma. The beneficial effects from roflumilast may be related to the SCF/c-kit pathway.
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: S W
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: C K
authors.initials: CK
authors.lastname: Park
authors.affiliation: Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: T J
authors.initials: TJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Y K
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: S S
authors.initials: SS
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: C K
authors.initials: CK
authors.lastname: Rhee
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: H K
authors.initials: HK
authors.lastname: Yoon
mesh_terms: D056151:Airway Remodeling / Q000276:immunology*; D000485:Allergens; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001549:Benzamides / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002908:Chronic Disease; D003521:Cyclopropanes / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020397:Goblet Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D000631:Aminopyridines; D018927:Anti-Asthmatic Agents; D001549:Benzamides; D003521:Cyclopropanes; D016207:Cytokines; C424423:Roflumilast; D007073:Immunoglobulin E; D006909:Hydroxyproline
keywords: airway inflammation; airway remodelling; asthma; roflumilast