| Project/Area Number |
14370738
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
OHUCHI Kazuo Tohoku University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (20006357)
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| Co-Investigator(Kenkyū-buntansha) |
HIRASAWA Noriyasu Tohoku University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究科, 助教授 (80181155)
ISHIHARA Kenji Tohoku University, Graduate School of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学研究科, 助手 (00312596)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | Bronchial epithelial cells / eosinophil granule protein / HDAC inhibitor / differentiation of eosinophil / ICAM-1 / E-cadherin / histamine / ヒスタミン / ヒスチジン脱炭酸酵素 / E-カドヘリン / アデノウイルス / 分化・増殖 / Adherence junction / E-cadherin / 12-O-tetradecanoylphorbol 13-acetate / NCI-H292 / BEAS-2B / HL-60 clone 15 / ヒストン脱アセチル化酵素阻害薬 / Eosinophils / Eosinophil-associated rebonuclease / RNase activity / Bactericidal activity / Epitherial cells / Interferon-gamma / STAT1 / Cycline-dependent kinase / 好酸球 / ケモカイン / 顆粒蛋白質 / RNase A / NF-κB |
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| Research Abstract |
Our findings in this project are as follows : 1. We prepared active recombinant protein of eosinophil granule protein, eosinophil associated ribonuclease (Ear)-1 and Ear-2. 2. The fraction of eosinophil granule protein showed no activity to induce epithelial cell injury. 3. Histone deacetylase (HDAC) inhibitor, apicidine and n-butyrate, induced eosinophil differentiation. 4. TPA and TNF-α induced the expression of ICAM-1 in human epithelial cell line NCI-H292 via the activation of NF-κB. In addition, the TPA-induce activation of NF-κB and expression of ICAM-1 were negatively regulated by p44/42 MAP kinase. 5. BEAS-2B cells, a human epithelial cell line, expressed E-cadherin as a result from the differentiation and morphological changes. 6. Histamine did not affect the proliferation and differentiation of epithelial cells although histamine enhanced angiogenesis via inducing VEGF production. These results suggested that eosinophil granule protein alone does not induce tissue injury. The activation of epithelial cells might be enhanced the cytotoxicity of eosinophils. In addition, histamine does not promote the repair and regeneration of epithelial tissues although histamine enhances fibrosis. Thus, histamine might promote remodeling of epithelial tissues.
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