Intratracheal delivery of hepatocyte growth factor directly attenuates allergic airway inflammation in mice.
Hepatocyte growth factor (HGF) has an important role in many biological events such as angiogenesis and cell proliferation, as well as anti-fibrotic and anti-apoptotic effects. In addition, we found that HGF suppresses antigen-induced immune responses in the airway by suppressing dendritic cell functions, using a HGF-producing plasmid vector. In the present study, we examined whether delivery of the HGF protein in the lung attenuates allergic airway inflammation in a mouse model. Generally, HGF is rapidly cleared from organs. So, to achieve the efficient delivery of HGF, we prepared a slow-releasing form by mounting recombinant human (rh) HGF protein in biodegradable gelatin hydrogels. BALB/c mice were immunized and then challenged with ovalbumin (OVA) to induce eosinophilic airway inflammation. Intratracheal delivery of a very small amount of gelatin-coupled rhHGF (0.3 microg) just once before the inhalation of OVA significantly suppressed eosinophilic airway inflammation. In addition, cytokine production in thoracic lymph nodes and the antigen-presenting capacity of lung CD11c+ cells were reduced. In contrast, delivery of 1.0 microg of rhHGF did not exhibit any significantly suppressive effect. These results suggest that the controlled release of rhHGF protein can suppress antigen-induced allergic immune responses in the lung. Therefore, HGF could be a novel therapeutic option for asthma.
Okunishi
Katsuhide
K
Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Sasaki
Oh
O
Okasora
Takahiro
T
Nakagome
Kazuyuki
K
Imamura
Mitsuru
M
Harada
Hiroaki
H
Matsumoto
Taku
T
Tanaka
Ryoichi
R
Yamamoto
Kazuhiko
K
Tabata
Yasuhiko
Y
Dohi
Makoto
M
D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D005780:Gelatin / Q000008:administration & dosage; D005782:Gels / Q000008:administration & dosage; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage
D003692:Delayed-Action Preparations; D005782:Gels; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D005780:Gelatin