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Prostaglandin E2 inhibits IL-23 and IL-12 production by human monocytes through down-regulation of their common p40 subunit.
- Source :
-
Molecular immunology [Mol Immunol] 2013 Mar; Vol. 53 (3), pp. 274-82. Date of Electronic Publication: 2012 Sep 14. - Publication Year :
- 2013
-
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.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Base Sequence
Cyclic AMP metabolism
DNA Primers genetics
Dendritic Cells drug effects
Dendritic Cells immunology
Dendritic Cells metabolism
Dinoprostone pharmacology
Down-Regulation drug effects
Humans
In Vitro Techniques
Interleukin-12 chemistry
Interleukin-12 genetics
Interleukin-23 chemistry
Interleukin-23 genetics
Lipopolysaccharides pharmacology
Macrophages drug effects
Macrophages immunology
Macrophages metabolism
Monocytes metabolism
Protein Subunits
RNA, Messenger genetics
RNA, Messenger metabolism
Interleukin-12 biosynthesis
Interleukin-23 biosynthesis
Monocytes drug effects
Monocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9142
- Volume :
- 53
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 22982753
- Full Text :
- https://doi.org/10.1016/j.molimm.2012.08.014