Docosahexaenoyl Serotonin, an endogenously formed n-3 fatty acid-serotonin conjugate has anti-inflammatory properties by attenuating IL-23–IL-17 signalling in macrophages

Authors Jean Paul ten Klooster , Raymond Pieters , Mieke Polanda , Zheng Wang , Renger Witkamp , Jocelijn Meijerink , Mark Boekschoten
Published in Biochimica et Biophysica Acta
Publication date 26 September 2016
Research groups Innovative Testing in Life Sciences and Chemistry
Type Article

Summary

Abstract from the article: "Conjugates of fatty acids and amines, including endocannabinoids, are known to play important roles as endogenous signaling molecules. Among these, the ethanolamine conjugate of the n-3 poly unsaturated long chain fatty acid (PUFA) docosahexaenoic acid (22:6n-3) (DHA) was shown to possess strong anti-inflammatory properties. Previously, we identified the serotonin conjugate of DHA, docosahexaenoyl serotonin (DHA-5-HT), in intestinal tissues and showed that its levels are markedly influenced by intake of n-3 PUFAs. However, its biological roles remain to be elucidated. Here, we show that DHA-5-HT possesses potent anti-inflammatory properties by attenuating the IL-23-IL-17 signaling cascade in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Transcriptome analysis revealed that DHA-5-HT down-regulates LPS-induced genes, particularly those involved in generating a CD4+ Th17 response. Hence, levels of PGE2, IL-6, IL-1β, and IL-23, all pivotal macrophage-produced mediators driving the activation of pathogenic Th17 cells in a concerted way, were found to be significantly suppressed by concentrations as low as 100–500 nM DHA-5-HT. Furthermore, DHA-5-HT inhibited the ability of RAW264.7 cells to migrate and downregulated chemokines like MCP-1, CCL-20, and gene-expression of CCL-22 and of several metalloproteinases. Gene set enrichment analysis (GSEA) suggested negative overlap with gene sets linked to inflammatory bowel disease (IBD) and positive overlap with gene sets related to the Nrf2 pathway. The specific formation of DHA-5-HT in the gut, combined with increasing data underlining the importance of the IL-23-IL-17 signaling pathway in the etiology of many chronic inflammatory diseases merits further investigation into its potential as therapeutic compound in e.g. IBD or intestinal tumorigenesis".

researchcomponents.publicationcontent.personslist.publicationauthors

  • Jean Paul ten Klooster | Researcher | Research group Innovative Testing in Life Sciences and Chemistry
    Jean Paul ten Klooster
    • Researcher
    • Research groups: Innovative Testing in Life Sciences and Chemistry
  • Raymond Pieters | Professor | Research group Innovative Testing in Life Sciences & Chemistry
    Raymond Pieters
    • Professor
    • Research groups: Innovative Testing in Life Sciences and Chemistry

Language English
Published in Biochimica et Biophysica Acta
Year and volume Volume 1861 Issue 12, Part A
ISBN/ISSN URN:ISSN:1388-1981
Key words Acyl serotonines, DHA, DHA-5-HT, Nrf2, Intestine, Endocannabinoids
Page range 2020-2028

Jean Paul ten Klooster

Jean Paul ten Klooster | Researcher | Research group Innovative Testing in Life Sciences and Chemistry

Jean Paul ten Klooster

  • Researcher
  • Research group: Innovative Testing in Life Sciences and Chemistry