Prostaglandin E2 induces IL‐23 production in bone marrow‐derived dendritic cells

Abstract

Interleukin‐23, a recently described cytokine produced by activated antigen‐presenting cells, including dendritic cells, is a p19/p40 heterodimer. The p40 subunit is shared with IL‐12, the major Th1‐driving cytokine, while p19 is distantly related to IL‐12 p35. IL‐23 has pro‐ inflammatory actions, inducing IL‐17 secretion from activated CD4+ T cells, and stimulating the proliferation of memory CD4+ T cells. Here, we examined the effects of PGE 2 , a well‐known immunomodulator, on the production of IL‐23 by bone marrow‐ derived dendritic cells (BM‐ DCs). Our results indicate that PGE 2 increases the production of functional IL‐23 from immature BM‐DCs in a time‐ and dose‐dependent manner. PGE 2 induces both the expression of p19 and p40, without affecting p35 expression. The effect of PGE 2 is mediated through the specific receptors EP2/4 and is mimicked by cAMP‐inducing agents, such as forskolin and dbcAMP. Although PGE 2 also induces IL‐1β and IL‐6 expression in non‐stimulated DCs, the stimulatory effect of PGE 2 on IL‐23 production is not mediated through IL‐1β or IL‐6. GM‐CSF, the pro‐ inflammatory cytokine required for the generation of BM‐DCs, amplifies the IL‐23 inducing activity of PGE 2 in a synergistic manner. Recent studies described both pro‐ and anti‐ inflammatory effects of PGE 2 , and our results suggest an additional mechanism for its pro‐ inflammatory role, particularly significant for autoimmune diseases, such as rheumatoid arthritis.