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 language | English |
|---|---|
| Pages (from-to) | 268-280 |
| Number of pages | 13 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 32 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2005 |
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Keywords
- Airway hyperresponsiveness
- Airway inflammation
- Airway remodeling
- Hepatocyte growth factor
- Transforming growth factor-β
ASJC Scopus subject areas
- Cell Biology
- Pulmonary and Respiratory Medicine
- Molecular Biology
Cite this
Hepatocyte growth factor attenuates airway hyperresponsiveness, inflammation, and remodeling. / Ito, Wataru; Kanehiro, Arihiko; Matsumoto, Kunio; Hirano, Atsushi; Ono, Katsuichiro; Maruyama, Hiromi; Kataoka, Mikio; Nakamura, Toshikazu; Gelfand, Erwin W.; Tanimoto, Mitsune.
In: American Journal of Respiratory Cell and Molecular Biology, Vol. 32, No. 4, 04.2005, p. 268-280.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hepatocyte growth factor attenuates airway hyperresponsiveness, inflammation, and remodeling
AU - Ito, Wataru
AU - Kanehiro, Arihiko
AU - Matsumoto, Kunio
AU - Hirano, Atsushi
AU - Ono, Katsuichiro
AU - Maruyama, Hiromi
AU - Kataoka, Mikio
AU - Nakamura, Toshikazu
AU - Gelfand, Erwin W.
AU - Tanimoto, Mitsune
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
KW - Airway hyperresponsiveness
KW - Airway inflammation
KW - Airway remodeling
KW - Hepatocyte growth factor
KW - Transforming growth factor-β
UR - http://www.scopus.com/inward/record.url?scp=20144388530&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20144388530&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2004-0058OC
DO - 10.1165/rcmb.2004-0058OC
M3 - Article
C2 - 15626778
AN - SCOPUS:20144388530
VL - 32
SP - 268
EP - 280
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 4
ER -