Inhibition of IL-6, TNF-α, and cyclooxygenase-2 protein expression by prostaglandin E2-induced IL-10 in bone marrow-derived dendritic cells

Several endogenously produced mediators, including cytokines such as IL-6, IL-10, and TNF-α and prostanoids such as prostaglandin E2 (PGE2), regulate dendritic cell (DC) function and contribute to immune homeostasis. In this study, we report that exogenous PGE2 enhances the production of IL-10 from bone marrow-derived DC (BM-DC). IL-6, but not TNF-α, release is enhanced by PGE2 in the presence of anti-IL-10, suggesting that endogenous IL-10 masks PGE2-induced IL-6. Furthermore, both exogenous IL-10 and PGE2 inhibit LPS-induced IL-6 and TNF-α, whereas selective inhibition of cyclooxygenase-2 (COX-2) or addition of anti-IL-10 causes the reverse effects. Exogenous IL-10, but not IL-6, dose-dependently suppresses COX-2 protein expression and PGE2 production, and TNF-α does not reverse this effect. In contrast, anti-IL-10 up-regulates prostanoid production by LPS-stimulated BM-DC. Taken together, our results show that in response to PGE2, BM-DC produce IL-10, which in turn down-regulates their own production of IL-6-, TNF-α-, and COX-2-derived prostanoids, and plays crucial roles in determining the BM-DC pro-inflammatory phenotype.