title: Growth factors temporally associate with airway responsiveness and inflammation in allergen-exposed mice.
abstract: BACKGROUND
  To clarify whether growth factors play critical roles in the development of airway hyperresponsiveness (AHR) and airway inflammation in the early stages of asthma, the relationship between growth factors and AHR and airway inflammation were analyzed in a mouse model of asthma.
  
  
  METHODS
  Following ovalbumin (OVA) sensitization and challenge, airway function, inflammation, cytokine and growth factor levels were monitored.
  
  
  RESULTS
  AHR to inhaled methacholine increased at 6 h, peaked at 48 h, and remained elevated for 14 days. IL-4 and IL-5 levels in bronchoalveolar lavage (BAL) fluid were increased at 6 h, peaked at 24 h, but returned to baseline quickly. IL-13 levels increased up to 14 days, peaking at 48 h. Increases in BAL fluid transforming growth factor-beta(1) and platelet-derived growth factor were observed at 12 h, and remained elevated at 14 days. Nerve growth factor levels were increased at 24-28 days. BAL fluid hepatocyte growth factor (HGF) was detected at 12 h, peaked at 24 h, and returned to baseline by 72 h. c-Met/HGF receptor was detected in the airways at 6 h, before HGF in the BAL, and continued to be observed 96 h after the last OVA challenge.
  
  
  CONCLUSIONS
  These data identify a temporal association between growth factor production and Th2 cytokine production and the kinetics of AHR. Growth factors may play important roles in the development of allergic airway inflammation and AHR even in the early stages of asthma, before remodeling is initiated.
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ito
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Katsuichiro
authors.initials: K
authors.lastname: Ono
authors.forename: Shinya
authors.initials: S
authors.lastname: Mizuno
authors.forename: Akio
authors.initials: A
authors.lastname: Yoshida
authors.forename: Hikari
authors.initials: H
authors.lastname: Koga
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Fuchimoto
authors.forename: Naruhito
authors.initials: N
authors.lastname: Kondo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tanimoto
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Kunio
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Mikio
authors.initials: M
authors.lastname: Kataoka
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
authors.forename: Arihiko
authors.initials: A
authors.lastname: Kanehiro
mesh_terms: D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D018836:Inflammation Mediators / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000485:Allergens; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D010047:Ovalbumin