Growth factors temporally associate with airway responsiveness and inflammation in allergen-exposed mice.
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.
Ito
Wataru
W
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Tanimoto
Mitsune
M
Ono
Katsuichiro
K
Mizuno
Shinya
S
Yoshida
Akio
A
Koga
Hikari
H
Fuchimoto
Yasuko
Y
Kondo
Naruhito
N
Tanimoto
Yasushi
Y
Kiura
Katsuyuki
K
Matsumoto
Kunio
K
Kataoka
Mikio
M
Nakamura
Toshikazu
T
Gelfand
Erwin W
EW
Kanehiro
Arihiko
A
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
D000485:Allergens; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D010047:Ovalbumin