Sensitivity difference to the suppressive effect of prostaglandin E2 among mouse strains: A possible mechanism to polarize Th2 type response in BALB/c mice

PGE, has been shown to play a prominent role in regulating Th1 and Th2 type responses. We studied the role of PGE, in IFN-gamma production by Staphylococcus aureus Cowan I-stimulated spleen cells from several mouse strains such as BALB/c, C3H/HeN, and C57BL/6, When spleen cells were pretreated with indomethacin (cyclooxygenase (COX)-1 and COX-2 inhibitor) or NS-398 (COX-2-specific inhibitor), S. aureus Cowan I -induced IFN-gamma production was increased more markedly in spleen cells from BALB/c mice than from C3H/HeN and C57BL/6 mouse. However, PGE(2) production was not significantly different among spleen cells from three mouse strains. When various concentrations of PGE(2) were exogeneously added to spleen cells, PGE(2) showed a stronger suppressive effect on IFN-gamma production in spleen cells from BALB/c mice than From other strains of mice. This suppressive effect of PGE(2) in BALB/c mice mainly depended on IL-12p70 production by APCs, More PGE(2) binding sites were Pound in BALB/c spleen cells than in C3H/HeN spleen cells, indicating that the sensitivity difference to the suppressive effect of PGE(2) was due to the difference of the number of PGE(2) receptors. The administration of NS-398 into BALB/c mice enhanced Ag-specific IFN-gamma production, but not IL-4 production. This effect is the same as IL-12 administration in vivo. From these results, we propose that the modulation of PGE(2) is important for Th1 activation via IFN-gamma and IL-12p70 production in vitro and in vivo and that PGE(2) is one of the pivot al factors in the Th2-dominant immune response in BALB/c mice.