title: Effects of zileuton on airway smooth muscle remodeling after repeated allergen challenge in brown Norway rats.
abstract: BACKGROUND
  Chronic asthma is characterized by airway inflammation and remodeling.
  
  
  OBJECTIVE
  This study aimed to evaluate the effects of zileuton on bronchial hyperresponsiveness, airway inflammation and airway smooth muscle (ASM) remodeling.
  
  
  METHODS
  Two experimental groups of brown Norway rats sensitized and repeatedly challenged with aerosolized ovalbumin (OA) were given oral zileuton (OA-zileuton group) and oral saline only (OA-saline group). A third, control group was sensitized and challenged by saline. The rats were anesthetized and paralyzed. Pulmonary function tests were performed at baseline and after varying doses of acetylcholine. Bronchoalveolar lavage fluid and lung tissues were examined.
  
  
  RESULTS
  Zileuton had beneficial effects on pulmonary function, airway inflammation and ASM remodeling in the OA-zileuton group compared to the OA-saline group. Zileuton inhibited an OA-stimulated increase in ASM by inhibiting hypertrophy, hyperplasia and increased extracellular matrix via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, thereby reducing cyclin D1 expression and attenuating bronchial hyperresponsiveness.
  
  
  CONCLUSIONS
  OA increases airway inflammation and ASM mass. Zileuton effectively prevents bronchial hyperresponsiveness, airway inflammation and ASM remodeling in sensitized rats through the PI3K/Akt pathway, which reduces cyclin D1 expression.
authors.affiliation: Chest Division, Departments of Internal Medicine and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan, ROC.
authors.forename: Wei-Ji
authors.initials: WJ
authors.lastname: Chen
authors.forename: Shwu-Fang
authors.initials: SF
authors.lastname: Liaw
authors.forename: Ching-Chi
authors.initials: CC
authors.lastname: Lin
authors.forename: Mei-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Feng-Ting
authors.initials: FT
authors.lastname: Chang
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects* / Q000276:immunology; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D020935:MAP Kinase Signaling System; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D012129:Respiratory Function Tests; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D000485:Allergens; D020024:Leukotriene Antagonists; D019869:Phosphatidylinositol 3-Kinases; C063449:zileuton; D006918:Hydroxyurea