Figure 4.

PGE₂-enhanced IL-33 production involves EPAC but not PKA or PI3K. A, IL-33 production by LPS-stimulated bmMFs (1.0 μg/ml) in the presence of selective cAMP analogs for PKA and EPAC. B, levels of IL-33 production by LPS-stimulated bmMFs with or without PGE₂ in the presence of the PKA inhibitor H89 (10.0 μm). C, effect of ESI09 (10.0 μm) on IL-33 production by LPS-stimulated bmMFs. D, effects of H89 and ESI09 alone and in combination on LPS-induced IL-33 production by WT bmMFs. E, effects of H89 and ESI09 on LPS-induced IL-6 production by the same samples as in D. F, effects of ESI09 on PGE₂-enhanced IL-33 production by bmMFs. G, effects of ESI09 on potentiation of IL-33 production by WT bmMFs stimulated with AE1-259-01 but not with AE-329. H, effect of wortmannin (1.0 μm) on LPS-induced IL-33 production and its potentiation by PGE₂. Data are presented as mean ± S.E. of at least three independent experiments. Statistical significance was determined using one-sample t test (comparing fixed 100%). p < 0.05 was considered statistically significant. *, p < 0.05; **, p < 0.005.