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Hepatocyte Growth Factor Attenuates Airway Hyperresponsiveness, Inflammation, and Remodeling

Second Department of Internal Medicine, Okayama University Medical School, Okayama; Biomedical Research Center, Osaka University Graduate School of Medicine, Osaka, Japan; and Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to Arihiko Kanehiro, M.D., Second Department of Internal Medicine, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. 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 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-ß (TGF-ß), platelet-derived growth factor, and nerve growth factor levels in BAL fluid. The expression of TGF-ß, 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-ß in BAL fluid. These data indicate that HGF may play an important role in the regulation of allergic airway inflammation, hyperresponsiveness, and remodeling.

Key Words: airway hyperresponsiveness • airway inflammation • airway remodeling • hepatocyte growth factor • transforming growth factor-ß

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