Sensitivity Difference to the Suppressive Effect of Prostaglandin E2 Among Mouse Strains: A Possible Mechanism to Polarize Th2 Type Response in BALB/c Mice

Abstract

PGE2 has been shown to play a prominent role in regulating Th1 and Th2 type responses. We studied the role of PGE2 in IFN-γ 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-γ production was increased more markedly in spleen cells from BALB/c mice than from C3H/HeN and C57BL/6 mouse. However, PGE2 production was not significantly different among spleen cells from three mouse strains. When various concentrations of PGE2 were exogeneously added to spleen cells, PGE2 showed a stronger suppressive effect on IFN-γ production in spleen cells from BALB/c mice than from other strains of mice. This suppressive effect of PGE2 in BALB/c mice mainly depended on IL-12p70 production by APCs. More PGE2 binding sites were found in BALB/c spleen cells than in C3H/HeN spleen cells, indicating that the sensitivity difference to the suppressive effect of PGE2 was due to the difference of the number of PGE2 receptors. The administration of NS-398 into BALB/c mice enhanced Ag-specific IFN-γ 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 PGE2 is important for Th1 activation via IFN-γ and IL-12p70 production in vitro and in vivo and that PGE2 is one of the pivotal factors in the Th2-dominant immune response in BALB/c mice.

Cyclooxygenase-2-Issued Prostaglandin E2 Enhances the Production of Endogenous IL-10, Which Down-Regulates Dendritic Cell Functions

“…Our finding is not in agreement with studies using human macrophages or DC; when considering the effects of IL-10 on DC phenotype and function, one should keep in mind that mouse and human DC populations are obviously not the same. Our results could be related to the high sensitivity of that lineage to the suppressive effect of PGE 2 , as was reported by Kuroda et al (58). However, in the data published by Kuroda, the distinctions between lineages exist only in terms of sensitivity, but there were no differences in terms of general orientation of the effects of PGE 2 on the immune response among the different mice.…”

Prostaglandin E2 down-regulates viable Bacille Calmette–Guérin-induced macrophage cytotoxicity against murine bladder cancer cell MBT-2in vitro

“…PGE 2 suppressed the activation of NK cells, lymphokine-activated killer cells and cytotoxic T cells by inhibiting IL-2 receptor expression on effector cell surfaces [8]. Recently, we also found that PGE 2 suppressed IFNg and IL-12 production by macrophages (9).…”

The Expression of Prostaglandin E Receptors EP2 and EP4 and Their Different Regulation by Lipopolysaccharide in C3H/HeN Peritoneal Macrophages

“…It is possible that the EP 4 -induced cAMP increase and the resultant activation of cAMP-dependent kinase during initiation of IL-12 gene activation may have a crucial effect on the following gene expression of this cytokine. A number of reports have established that the cAMPdependent pathway inhibits IL-12 production at the transcriptional level, possibly by affecting cAMP response element (CRE) binding complexes (31)(32)(33). Thus, EP 4 gene expression is down-regulated upon stimulation with LPS, but this receptor appears to have a pivotal role in autocrine regulation of cytokine release, and EP 2 might contribute to extend the inhibitory effect of PGE 2 on a dayscale duration.…”