| Project/Area Number |
17590395
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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 |
Bacteriology (including Mycology)
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| Research Institution | Kumamoto university |
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Principal Investigator |
TAMURA Fumio Kumamoto University, Graduate School Medical Science, Gastroenterology and Hepatology, Assistant, 大学院医学薬学研究部, 助手 (20359962)
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| Co-Investigator(Kenkyū-buntansha) |
AKAIKE Takaaki Kumamoto university, Graduate School of Medical Science, Microbiology, Professor, 大学院医学薬学研究部, 教授 (20231798)
AKUTA Teruo Kumamoto university, Graduate School of Medical Science, Microbiology, Assistant, 大学院医学薬学研究部, 助手 (00346975)
SASAKI Yutaka Kumamoto university, Graduate School of Medical Science, Gastroenterology and Hepatology, Professor, 大学院医学薬学研究部, 教授 (70235282)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Bacterial Portease / Apoptosis / a2-macrogrobulin / MMP |
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| Research Abstract |
Recently it was shown that streptococcal pyrogenic exotoxin B (SpeB), a thiol protease derived from group A Streptococcus (GAS) could cause an increase in apoptotic cell death. The present study is aimed to clarify the mechanism of apoptosis induced by a variety of bacterial proteases. When human monocyte- like U937 cells were treated with SpeB, Serratiamarcescens 56kDa protease, or Pseudomonas aeruginosa elastase, all these bacterial proteases induced apoptosis in U937 cells. Serratial protease was internalized by the cells in culture as a complex form with α2-macroglobulin (a2-M) via α2-M receptor, which resulted in apoptosis. Furthermore, expressions of Bcl-2, c-lAP1 and hsp70, which were anti-apoptotic proteins, were investigated by Western blot analysis after treatment of U937 cells with serratial protease. Serratial protease degraded c-IAP1 protein more selectively than others intracellular proteins. We previously reported that some bacterial proteases could activate human MMPs, which may play important roles in tissue degeneration, and in the present study, SpeB also was confirmed activation of MMPs. We investigated whether SpeB-activatedMMPcouldprocessTNF-a andFasligandfromcellmembranetocause apoptotic cell death. SpeB activated with proMM P-9, and soluble TN F-a and Fas ligand were released from culture cells by this activated MMP-9. SpeB-dependent induction of extensive apoptosis and its related proapoptotic molecules, e.g., soluble TNF-a, Fas ligand, and MMPs, was evident in a murine model of severe GAS infections. These results suggested that bacterial proteases induce apoptotic cell death either via α2-M receptor, or via activation of MMPs.
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