|Budget Amount *help
¥3,500,000 (Direct Cost : ¥3,500,000)
Fiscal Year 2001 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 2000 : ¥2,500,000 (Direct Cost : ¥2,500,000)
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.