| Project/Area Number |
12670196
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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 |
Experimental pathology
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| Research Institution | Niigata University |
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Principal Investigator |
YAMAMOTO Takashi Graduate School of Medical and Dental Sciences, Niigata University, Assiatant, 大学院・医歯学総合研究科, 助手 (70313517)
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| Co-Investigator(Kenkyū-buntansha) |
HASEGAWA Go Graduate School of Medical and Dental Sciences, Niigata University, Lecturer, 大学院・医歯学総合研究科, 講師 (90251800)
NAITO Makoto Graduate School of Medical and Dental Sciences, Niigata University, Professor, 大学院・医歯学総合研究科, 教授 (30045786)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | macrophages / Apoptosis inhibitor expressed by macrophages (AIM) / apoptosis / knockout mice / granuloma / C. parvum / host defence / lymphocytes / 肉芽腫 |
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| Research Abstract |
Apoptosis inhibitor expressed by macrophages (AIM) inhibits apoptosis of CD4+CD8+ double-positive (CD4/CD8 DP) thymocytes, and supports the viability of these cells on the thymic selection. However, pleiotropic functions of AIM have been suggested. In this report, heat-killed Corynebacterium parvum (C. parvum) was injected to mice carrying the homozygous mutation (AIM -/-) and wild-type (AIM +/+) mice for the formation of hepatic granulomas. In AIM -/- mice, the size and the number of C. parvum-induced granulomas in the liver were larger than those in wild type mice. Resorption of granulomas was delayed in the knockout mice and the production of IL-12 was more prominent in the knockout mice than wild type mice. In the wild type mouse liver, expression of AIM mRNA was increased after P. acnes injection. In situ hybridization demonstrated that AIM mRNA was expressed in Kupffer cells and macrophages in the granulomas. In the early stage of granuloma formation, larger numbers of T cells and NKT cells underwent apoptosis in the knockout mice, suggesting that AIM prevents apoptosis of NKT cells and T cells in C. parvum-induced inflammation. In the late stage, recovery of NKT cells in the liver of knockout mice was less remarkable than wild type mice. These results suggest that AIM provides beneficial effects for the formation and resorption of granulomas through NKT cell- and T cell-mediated mechanisms.
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