Prostaglandin E2 modulates dendritic cell function via EP2 and EP4 receptor subtypes

We have reported previously that PGE(2) inhibits dendritic cells (DC) functions. Because E prostanoid receptor (EPR) subtypes involved in this action are unknown, expression and functions of these receptors were examined in DC. Western blot and flow cytometry analyses showed that all EPRs were coexpressed in DC. In a dose-dependent manner, lipopolysaccharide (LPS) enhanced EP2R/EP4R but not EP1R/EP3R expressions. NS-398, a cyclooxygenase (COX)-2-selective inhibitor, suppressed LPS-enhanced EP2R/EP4R expression, suggesting that COX-2-issued prostaglandin E-2 (PGE(2)) modulates DC function through stimulation of specific EPR subtypes. Using selective agonists, we found that butaprost, an EP2R agonist, and PGE(1) alcohol, an EP2R and EP2R/EP4R agonist, inhibited major histocompatibility complex class II expression and enhanced interleukin-10 production from DC. However, no effect was observed with sulprostone and 17-phenyl-omega-trinor-PGE(2) selective agonists for EP1R and EP1R/EP3R, respectively. Treatment of DC with dibutyryl cyclic adenosine monophosphate (cAMP), an analog of cAMP, mimics PGE(2)-induced, inhibitory effects. Taken together, our data demonstrate that EP2R/EP4R are efficient for mediating PGE(2)-induced modulation of DC functions.