Hepatocyte growth factor attenuates airway hyperresponsiveness, inflammation, and remodeling

Wataru Ito, Arihiko Kanehiro, Kunio Matsumoto, Atsushi Hirano, Katsuichiro Ono, Hiromi Maruyama, Mikio Kataoka, Toshikazu Nakamura, Erwin W. Gelfand, Mitsune Tanimoto

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53 Citations (Scopus)

Abstract

Hepatocyte growth factor (HGF) is known to influence a number of cell types and their production of regulatory cytokines. We investigated the potential of recombinant HGF to regulate not only the development of allergic airway inflammation and airway hyperresponsiveness (AHR), but also airway remodeling in a murine model. Administration of exogenous HGF after sensitization but during ovalbumin challenge significantly prevented AHR, as well as eosinophil and lymphocyte accumulation in the airways; interleukin (IL)-4, IL-5, and IL-13 levels in bronchoalveolar lavage (BAL) fluid were also significantly reduced. Further, treatment with HGF significantly suppressed transforming growth factor-β (TGF-β), platelet-derived growth factor, and nerve growth factor levels in BAL fluid. The expression of TGF-β, the development of goblet cell hyperplasia and subepithelial collagenization, and the increases in contractile elements in the lung were also reduced by recombinant HGF. Neutralization of endogenous HGF resulted in increased AHR as well as the number of eosinophils, levels of Th2 cytokines (IL-4, IL-5, and IL-13) and TGF-β in BAL fluid. These data indicate that HGF may play an important role in the regulation of allergic airway inflammation, hyperresponsiveness, and remodeling.

Original languageEnglish
Pages (from-to)268-280
Number of pages13
JournalAmerican journal of respiratory cell and molecular biology
Volume32
Issue number4
DOIs
Publication statusPublished - Apr 1 2005

Keywords

  • Airway hyperresponsiveness
  • Airway inflammation
  • Airway remodeling
  • Hepatocyte growth factor
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Ito, W., Kanehiro, A., Matsumoto, K., Hirano, A., Ono, K., Maruyama, H., Kataoka, M., Nakamura, T., Gelfand, E. W., & Tanimoto, M. (2005). Hepatocyte growth factor attenuates airway hyperresponsiveness, inflammation, and remodeling. American journal of respiratory cell and molecular biology, 32(4), 268-280. https://doi.org/10.1165/rcmb.2004-0058OC