Growth factors temporally associate with airway responsiveness and inflammation in allergen-exposed mice

Wataru Ito, Mitsune Tanimoto, Katsuichiro Ono, Shinya Mizuno, Akio Yoshida, Hikari Koga, Yasuko Fuchimoto, Naruhito Kondo, Yasushi Tanimoto, Katsuyuki Kiura, Kunio Matsumoto, Mikio Kataoka, Toshikazu Nakamura, Erwin W. Gelfand, Arihiko Kanehiro

Research output: Contribution to journalArticle

13 Citations (Scopus)


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-β1 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.

Original languageEnglish
Pages (from-to)324-339
Number of pages16
JournalInternational archives of allergy and immunology
Issue number4
Publication statusPublished - Mar 1 2008



  • Airway hyperresponsiveness
  • Growth factor
  • Hepatocyte growth factor
  • Transforming growth factor-β
  • c-Met/hepatocyte growth factor receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Ito, W., Tanimoto, M., Ono, K., Mizuno, S., Yoshida, A., Koga, H., Fuchimoto, Y., Kondo, N., Tanimoto, Y., Kiura, K., Matsumoto, K., Kataoka, M., Nakamura, T., Gelfand, E. W., & Kanehiro, A. (2008). Growth factors temporally associate with airway responsiveness and inflammation in allergen-exposed mice. International archives of allergy and immunology, 145(4), 324-339.