| Project/Area Number |
15590444
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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 |
Immunology
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| Research Institution | University of Occupational and Environmental Health(UOEH) |
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Principal Investigator |
YAMASHITA Uki UOEH, Sch. Med., Professor, 医学部, 教授 (00028680)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIURA Tsutomu UOEH, Sch. Med., Assistant Prof., 医学部, 講師 (40131924)
YOSHIDA Yasuhiro UOEH, Sch. Med., Res. Associate, 医学部, 助手 (10309958)
KURODA Etsushi UOEH, Sch. Med., Res. Associate, 医学部, 助手 (10299604)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | BALB / c mouse / macrophage / prostaglandin / PLA_2 / PGE synthase / IL-3 / IL-12 / IFN-γ / arachidonic acid |
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| Research Abstract |
There are two subsets of helper T cells, Th1 and Th2. Th1 mediates cellular immunity, and Th2 mediates humoral immunity. Generally, in BALB/c mice, Th2 is more easily activated by immunization and infection when compared with OH/He and C57BL/6 mice, and higher level of serum IgE and eosinophilia are induced. However, the precise mechanism of Th2 activation in BALB/c mice is not fully understood. Prostaglandin E_2 (PGE_2) is reported to have immunosuppressive activity, especially on Th1-mediated immune responses. We have studied the role of PGE_2 for the regulation of immune responses. In this project we studied the strain difference of PGE_2 production by macrophages and the genetic mechanism to induce this difference using BALB/c and C57BL/6 mice.
The obtained results are as follows : (1)Maerophages from BALB/c mice produced larger amounts of PGE_2 than that from C57BL/6 mice. (2)In propotion with the amounts of PGE2, macrophages from BALB/c mice produced smaller amounts of IL-12 and s
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howed lower accessory function for T cell activation. (3)Macrophages from BALB/c mice produced larger amounts of arachidonic acid and the expression of secretory type of phospholypase A_2 was enhanced, although there is no strain difference in the expression of cyclooxygenase-2 between BALB/c and C57BL/6 macrophages. (4)The expression of microsomal PGE synthase, final step of enzyme in PGE_2 synthesis, was also enhanced in BALB/c macrophages. (5)IL-3-induced bone marrow-derived macrophages from BALB/c mice also produced larger amounts of PGE_2 than that from C57BL/6 mice. Finally we studied the gene expression by microarray method using IL-3-induced bone marrow-derived macrophages and detected 20 genes which showed significant difference in its expression between BALB/c and C57BL/6 macrophages.
In conclusion, macrophages from BALB/c mice produced larger amounts of PGE_2 through enhanced expression of secretory type of phospholypase A_2 and microsomal PGE synthase. As a result, IL-12 production by macrophages was reduced, and finally Th1 activation was reduced. Furthemore, the difference of macrophage functions were determined at the level of precursor cells in the bone marrow. Less
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