2. Academic Validation
  3. Docosahexaenoyl serotonin emerges as most potent inhibitor of IL-17 and CCL-20 released by blood mononuclear cells from a series of N-acyl serotonins identified in human intestinal tissue

Docosahexaenoyl serotonin emerges as most potent inhibitor of IL-17 and CCL-20 released by blood mononuclear cells from a series of N-acyl serotonins identified in human intestinal tissue

  • Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Sep;1862(9):823-831. doi: 10.1016/j.bbalip.2017.05.008.
Ya Wang 1,  Michiel G J Balvers 2,  Henk F J Hendriks 3,  Tessa Wilpshaar 4,  Tjarda van Heek 5,  Renger F Witkamp 6,  Jocelijn Meijerink 7
Affiliations

Affiliations

  • 1 Division of Human Nutrition, Wageningen University, PO Box 17, 6700 AA Wageningen, The Netherlands; Laboratory of Food Chemistry, Wageningen University, PO Box 17, 6700 AA Wageningen, The Netherlands. Electronic address: [email protected].
  • 2 Division of Human Nutrition, Wageningen University, PO Box 17, 6700 AA Wageningen, The Netherlands. Electronic address: [email protected].
  • 3 Top Institute Food and Nutrition, Nieuwe Kanaal 9A, 6709 PA, Wageningen, The Netherlands. Electronic address: [email protected].
  • 4 Division of Human Nutrition, Wageningen University, PO Box 17, 6700 AA Wageningen, The Netherlands. Electronic address: [email protected].
  • 5 Department of Surgery, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716 RP, Ede, The Netherlands. Electronic address: [email protected].
  • 6 Division of Human Nutrition, Wageningen University, PO Box 17, 6700 AA Wageningen, The Netherlands. Electronic address: [email protected].
  • 7 Division of Human Nutrition, Wageningen University, PO Box 17, 6700 AA Wageningen, The Netherlands. Electronic address: [email protected].
PMID: 28526351 DOI: 10.1016/j.bbalip.2017.05.008
Abstract

Fatty acid amides (FAAs), conjugates of fatty acids with ethanolamine, mono-amine neurotransmitters or Amino acids are a class of molecules that display diverse functional roles in different cells and tissues. Recently we reported that one of the serotonin-fatty acid conjugates, docosahexaenoyl serotonin (DHA-5-HT), previously found in gut tissue of mouse and pig, attenuates the IL-23-IL-17 signaling axis in LPS-stimulated mice macrophages. However, its presence and effects in humans remained to be elucidated. Here, we report for the first time its identification in human intestinal (colon) tissue, along with a series of related N-acyl serotonins. Furthermore, we tested these fatty acid conjugates for their ability to inhibit the release of IL-17 and CCL-20 by stimulated human peripheral blood mononuclear cells (PBMCs). Serotonin conjugates with palmitic acid (PA-5-HT), stearic acid (SA-5-HT) and oleic acid (OA-5-HT) were detected in higher levels than arachidonoyl serotonin (AA-5-HT) and DHA-5-HT, while eicosapentaenoyl serotonin (EPA-5-HT) could not be quantified. Among these, DHA-5-HT was the most potent in inhibiting IL-17 and CCL-20, typical Th17 pro-inflammatory mediators, by Concanavalin A (ConA)-stimulated human PBMCs. These results underline the idea that DHA-5-HT is a gut-specific endogenously produced mediator with the capacity to modulate the IL-17/Th17 signaling response. Our findings may be of relevance in relation to intestinal inflammatory diseases like Crohn's disease and Ulcerative colitis.

Keywords

CCL-20; Docosahexaenoyl serotonin; Endocannabinoids; IL-17; Inflammatory bowel disease (IBD); Th17.

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