Prostaglandin E2 inhibits IL-23 and IL-12 production by human monocytes through down-regulation of their common p40 subunit

Mol Immunol. 2013 Mar;53(3):274-82. doi: 10.1016/j.molimm.2012.08.014. Epub 2012 Sep 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 / biosynthesis*
  • Interleukin-12 / chemistry
  • Interleukin-12 / genetics
  • Interleukin-23 / biosynthesis*
  • Interleukin-23 / chemistry
  • Interleukin-23 / genetics
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism
  • Monocytes / drug effects*
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Protein Subunits
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • DNA Primers
  • Interleukin-23
  • Lipopolysaccharides
  • Protein Subunits
  • RNA, Messenger
  • Interleukin-12
  • Cyclic AMP
  • Dinoprostone