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Published ahead of print on December 30, 2004, doi:10.1165/rcmb.2004-0058OC

Am. J. Respir. Cell Mol. Biol., Volume 32, Number 4, April 2005, 268-280

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Submitted on February 20, 2004
Revised on December 30, 2004

Hepatocyte Growth Factor Attenuates Airway Hyperresponsiveness, Inflammation and Remodeling

Wataru Ito1, Arihiko Kanehiro2*, Kunio Matsumoto3, Atsushi Hirano3, Katsuichiro Ono3, Hiromi Maruyama3, Mikio Kataoka3, Toshikazu Nakamura2, Erwin W Gelfand4, and Mitsune Tanimoto3

1 Second Department of Internal Medicine, Okayama University Medical School, Okayama, Japan; Department of Pediatrics, National Jewish Center, Denver, CO, USA, 2 Biomedical Research Center, Osaka University Graduate School of Medicine, Osaka, Japan, 3 Second Department of Internal Medicine, Okayama University Medical School, Okayama, Japan, 4 Department of Pediatrics, National Jewish Center, Denver, CO, USA

* To whom correspondence should be addressed. E-mail: akanehir{at}md.okayama-u.ac.jp.

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 OVA challenge significantly prevented AHR, as well as eosinophil and lymphocyte accumulation in the airways; IL-4, IL-5, and IL-13 levels in BAL fluid were also significantly reduced. Further, treatment with HGF significantly suppressed transforming growth factor-beta (TGF-{beta}), platelet-derived growth factor (PDGF) and nerve growth factor (NGF) levels in BAL fluid. The expression of TGF-{beta}, and the development of goblet cell hyperplasia, 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-{beta} in BAL fluid. These data indicate that HGF may play an important role in the regulation of allergic airway inflammation, hyperresponsiveness, and remodeling.




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