| Project/Area Number |
13670592
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
DOHI Makoto The University of Tokyo, Health Service Center, Research Associate, 保健管理センター, 助手 (60222155)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Kazuhiko The University of Tokyo, Allergy and Rheumatology, Professor, 医学部附属病院, 教授 (80191394)
TANAKA Ryoichi The University of Tokyo, Allergy and Rheumatology, Research Associate, 医学部附属病院, 助手 (60272556)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Bronchial asthma / Hepatocyte growth factor / Repair factor / 動物モデル / 気道過敏性 / 気管支上皮細胞 / 気道炎症 / 肝細胞増殖因子(MGF) |
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| Research Abstract |
We investigated a role of hepatocyte growth factor (HGF) in bronchial asthma with experimental model.
1) Serial change in serum HGF expression
BALD/c mice were immunized with ovalubmin (OVA) antigen, then were nebulized with OVA solution. to induce asthmatic response. HGF concentration in. the lung and serum were serially measured. Systemic sensitization with antigen induced an increase in lung HGF content. Along with the development of airway inflammation, HGF content further increased.
2) Study on the induction of HGF-producing plasmid vector in vivo
First, intra-muscular injection of the plasmid failed to produce HGF protein. Next we injected the plasmid with cationic liposome directly in the lung. Although certain amount of HGF was measurable in lung extract by this route of injection, it provoked non-specific inflammation in the lung, and neutrophils infiltrated into the lung. So this method would not be applicable for humans. Next, intra-dermal injection was tried, but it did not produce HGF expression.
As a forth trial, we applied intravenous administration of the plasmid. This achieved a high serum HGF concentration of 50〜80 ng/ml, and the increase in serum concentration continued for 5 about days.
3) Finally, we investigated a role of HGF in vivo in a mouse model of asthma by intravenous injection system. BALB/c mice were immunized with.ovalubmin OVA, then were nebulized with OVA solution for 3 consecutive days. Twenty four hours after the final inhalation, samples were analyzed. HGF-producing vector or control vector was administered before the first OVA inhalation by a single injection. Induction of HGF-producing vector in vivo suppressed the increase in airway hyperreactivity as well as eosinophilic airway inflammation. These results, for the first time, clarified an inhibitory role of HGF in allergic reaction in the airway. For further progress analyses of the mechanisms of the suppression should be investigated.
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