title: Prostaglandin E2 inhibits IL-23 and IL-12 production by human monocytes through down-regulation of their common p40 subunit.
abstract: The heterodimeric cytokine IL-23 is important for the maintenance of Th17 cells, which are pivotal mediators of autoimmune diseases like rheumatoid arthritis, colitis, and multiple sclerosis. Prostaglandin E2 (PGE2) is a soluble regulator of inflammation that has both pro- and anti-inflammatory properties. PGE2 has been shown to elevate the IL-23 production by dendritic cells (DC). Monocytes are also producers of IL-23 but the effect of PGE2 on IL-23 production by human monocytes has hardly been investigated. We show here that PGE2 blocks the production of IL-23 by LPS-stimulated monocytes in an IL-10 and IL-1β independent manner. This effect was due to the down-regulation of the p40 subunit of IL-23 on mRNA and protein level. The p40 subunit is shared by IL-12 and, consistently, PGE2 also lowered the IL-12 production by monocytes. These effects of PGE2 were cAMP-dependent since the cAMP enhancer forskolin strongly reduced IL-23 and IL-12 production by monocytes. Taken together, PGE2 acts in an anti-inflammatory manner by lowering IL-23 production by monocytes while it has the opposite effect in DC. Our data may help to reconcile controversial point of views on the pro- and anti-inflammatory nature of PGE2 by making a strong case for a cell type-dependent function.
authors.affiliation: Division of Immunology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany.
authors.forename: Khalid W
authors.initials: KW
authors.lastname: Kalim
authors.forename: Marcus
authors.initials: M
authors.lastname: Groettrup
mesh_terms: D001483:Base Sequence; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D053759:Interleukin-23 / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D017931:DNA Primers; D053759:Interleukin-23; D008070:Lipopolysaccharides; D021122:Protein Subunits; D012333:RNA, Messenger; D018664:Interleukin-12; D000242:Cyclic AMP; D015232:Dinoprostone