| Project/Area Number |
12670109
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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 |
General medical chemistry
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| Research Institution | SHINSHU UNIVERSITY |
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Principal Investigator |
SAGARA Junji Shinshu Universidy School of medicine, Associate Professor, 医学部, 助教授 (10225831)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGUCHI Shunichiro Shinshu Universidy School of Medicine, Professor, 医学部, 教授 (60117166)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | apoptosis / ASC / PYRIN / caspase-1 / interleukine-1β / interleukine-18 / inflammation / innate immunity / NF-KB / 炎症疾患 / Pyrin / Toll-like receptor / 感染 / 細胞死 / ガン / メチレーション / pyrin / CARD |
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| Research Abstract |
We showed that apoptosis-associated speck-like protein containing a Caspase recruitment domain (ASC) was an adaptor protein that was composed of two protein-protein interaction domains, a PYRIN domain, and a caspase-recruitment domain CARD. ASC belongs to a large family of proteins that contain a Pyrin, AIM, ASC, and death domain-like (PYRIN) domain (also known as PAAD and DAPIN). Recent data have suggested that ASC functions as an adaptor protein linking various PYRIN-family proteins to pathways involved in nuclear factor (NF)-kappaB and pro-Caspase-1 activation. Next, we focused on the expression of ASC in neutrophils. Immunohistochemical study showed that ASC is increased in neutrophils in severe inflammatory sites of gangrenous appendicitis. Also showed that ASC was increased in neutrophils exhibiting-characteristic phenotypes for apoptosis. These findings suggest that up-regulation of ASC is closely associated with inflammation and apoptosis in neutrophils. ASC also modulates diverse NF-kappaB induction pathways by acting upon the IKK complex, implying a broad role for this and similar proteins containing PYRIN domains in regulation of inflammatory responses.
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