| Project/Area Number |
18591618
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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 |
Cerebral neurosurgery
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
YAMASHITA Uki University of Occupational and Environmental Health, Japan, Sch. Med., Professor (00028680)
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| Co-Investigator(Kenkyū-buntansha) |
黒田 悦史 産業医科大学, 医学部, 助手 (10299604)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,740,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | glioma / microglia / prostaglandin / immunosuppression / マウス |
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| Research Abstract |
Malignant glioma is a malignant tumor originated in the central nervous system and several therapeutic approaches have been used for the treatment of glioma. However, the prognosis of malignant glioma is poor. There are reports to show that the immune responses against glioma are induced in the patients. However, it is difficult to treat glioma by immunological technique alone. One of the reasons to be difficult in the treatment of glioma by immunological techniques is considered to be due to the immunosuppression in glioma-bearing hosts. Accordingly it is important to study the mechanism of immunosuppression in glioma-bearing hosts and to improve the immunosuppressive states to induce effective immune responses in glioma patients. Previously we found that the coculture of macrophages and glioma induced the production of large amounts of prostaglandin (PG) by macrophages. Furthermore, cytokine productions such as IL-12 and TNF, important for tumor immunity, were depressed in these macr
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ophages. These results suggest that glioma stimulates macrophages to produce PG which induce immunosuppressive states.
In this research project we studied the role of microglia, which is a macrophage in the central nervous system, in the immune responses, and the mechanism of immunosuppression in glioma-bearing hosts. The obtained results are:
1) Microglia was induced by in vitro culture of the brain from neonatal mice.
The coculture of microglia with glioma induced the production of PG by microglia.
On the other hand TNF production by this microglia was depressed.
2) Microglia from PG synthase-deficient mice did not produce PG, and TNF-production was not suppressed.
3) In PG synthase-deficient mice, the growth of glioma was suppressed, but the effective immune responses against glioma were induced.
These results suggest that glioma induces immunosuppressive states by producing PG in microglia, and it is possible to induce effective immune responses against glioma by controlling PG production in microglia. Less
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