2001 Fiscal Year Final Research Report Summary
Role ofprostaglandin in the selective activation of Th2 cells in BALB/c mice
| Project/Area Number |
12670311
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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 |
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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)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Th1 / Th2 / IFN-y / IL-12 / MDC / prostaglandin / BALB / c mouse |
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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 C3H/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 studied the role of PGE_2 in the production of cytokines and chemokines by spleen cells and peritoneal exudates cells stimulated with Staphyhcoccus aureus Cowan I (SAC) using BALB/c, C3H/HeN and C57BL/6 mice and obtained the following results. (1)The treatment of spleen cells with indomethacine, cyclooxygenase (COX)-1 and COX-2 inhibitor, or NS-398, COX-2 specific inhibitor, more clearly enhanced IFN-γ-production by spleen cells from BALB/c mice than from C3H/He and CSTBL/c mice. (2)The amount of PGEz after SAC-stimulation is higher in BALB/c mice than C3H/He and C57BL/6 mice. (3)The addition of PGE_2 into the spleen cell culture more clearly suppressed IFN-γ and IL42p70 production by BALB/c spleen cells than C3H/HeN and C57BL spleen cells. (4)The in vivo administration of NS-398 into BALB/c mice enhanced antigen-specific IFN-γ production and its enhancing activity was similar to that of IL-12.(5)Macrophage-derived chemokine (MDC) production is also higher in BALB/c mice, and its production is further upregulated by PGE_2. These results suggest that PGE_2 plays an important role for the preferential activation of Th2 in BALB/c mice by suppressing IL-12p70 production and enhancing MDC production by antigen-presenting cells.
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