期刊
FASEB JOURNAL
卷 18, 期 9, 页码 1318-+出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.03-1367fje
关键词
PGE(2); inflammation; EP2/EP4 receptors
资金
- NIAID NIH HHS [AI47325, AI052306] Funding Source: Medline
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-1beta and IL-6 expression in non-stimulated DCs, the stimulatory effect of PGE(2) on IL-23 production is not mediated through IL-1beta 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.
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