Prostaglandin E2 induces IL-23 production in bone marrow-derived dendritic cells.
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 PGE2, a well-known immunomodulator, on the production of IL-23 by bone marrow- derived dendritic cells (BM-DCs). Our results indicate that PGE2 increases the production of functional IL-23 from immature BM-DCs in a time- and dose-dependent manner. PGE2 induces both the expression of p19 and p40, without affecting p35 expression. The effect of PGE2 is mediated through the specific receptors EP2/4 and is mimicked by cAMP-inducing agents, such as forskolin and dbcAMP. Although PGE2 also induces IL-1beta and IL-6 expression in non-stimulated DCs, the stimulatory effect of PGE2 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 PGE2 in a synergistic manner. Recent studies described both pro- and anti-inflammatory effects of PGE2, and our results suggest an additional mechanism for its pro-inflammatory role, particularly significant for autoimmune diseases, such as rheumatoid arthritis.
Sheibanie
Amir F
AF
Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102, USA.
Tadmori
Iman
I
Jing
Huie
H
Vassiliou
Evros
E
Ganea
Doina
D
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001168:Arthritis / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D016595:Misoprostol / Q000494:pharmacology; D010954:Plasmacytoma / Q000473:pathology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000502:physiology; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
D017077:Culture Media, Conditioned; C508841:Il23a protein, mouse; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D008070:Lipopolysaccharides; D011448:Prostaglandin Antagonists; D021122:Protein Subunits; D011956:Receptors, Cell Surface; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016595:Misoprostol; D018664:Interleukin-12; D005576:Colforsin; C016767:sulprostone; D003994:Bucladesine; D000242:Cyclic AMP; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone