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Background and purpose: Dendritic cells (DCs) are the most potent antigen-presenting cells and play major roles in both the induction of primary immune responses and tolerance.Prostaglandin E2 (PGE2) is a very potent lipid mediator and regulates the function of DCs.The molecular mechanisms involved in regulation DC maturation and activation by PGE2 are not elucidated.In the present study we investigate the mechanisms of PGE2-receptors (EP) signaling pathway promote DC maturation and activation and the effects of a novel compound paeoniflorin-6-O-benzene sulfonate (code is CP-25).Methods: EP expression on rat bone marrow (BM) derived-(BMDC) was determined by western blotting.Effects of PGE2 on DC maturation in conjunction with TNFα were assessed.Allogeneic T cell stimulation by BMDC was determined by mixed leukocyte cultures.The ability of endocytosis FITC-dextran and surface molecule expression were analyzed by flow cytometry analysis.The level of cytokine was examined by ELISA from culture supematants.Results: PGE2 synergized with proinflammatory cytokines TNFα promote BMDC maturation and activation through the EP4-cAMP/PI3K signaling.Treatment of DCs induced by PGE2 with CP-25 slightly increased the endocytic capacity.CP-25 inhibited the potency of DC induced by EP4 receptor agonist CAY10598 to stimulate allogeneic T cells by.In line, CAY10598-induced upregulation of DC surface activation markers and production of IL-23 was significantly inhibited by CP-25 in a concentration-dependent.Conclusions: EP4-cAMP/PI3K signaling is efficient for mediating PGE2 induced regulation of BMDC maturation and activation.Inhibition of CP-25 on DCs maturation and activation via intervening PGE2-EP4 pathway may significantly contribute to the immunosuppressive profile of CP-25 when applied for RA and other immune cell mediated disorders.