کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5508537 | 1537697 | 2016 | 41 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Docosahexaenoyl serotonin, an endogenously formed n-3 fatty acid-serotonin conjugate has anti-inflammatory properties by attenuating IL-23-IL-17 signaling in macrophages
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کلمات کلیدی
DHEAFAAHFAAGSEANOS2COX-2Nrf2FDRAEAAA-5-HTTRPV1LPSnESOEA - OASFatty acid amides - آمید های اسید چربFatty acid amide hydrolase - اسید آمینه هیدرولاز اسید چربdocosahexaenoic acid (22:6n-3) - اسید داکوزاگزائنیک (22: 6n-3)endocannabinoids - اندوکانبایوئید هاinterleukin - اینترلوکینGene-set enrichment analysis - تجزیه و تحلیل غنی سازی ژنDHA - دوکوساهگزائنوئیک اسیدIntestine - رودهcyclooxygenase 2 - سیکلوکوکسیژناز 2lipopolysaccharide - لیپوپلی ساکاریدfalse discovery rate - میزان کشف کاذبnormalized enrichment score - نمره غنی سازی نرمال شدهNitric oxide - نیتریک اکسیدnitric oxide synthase 2 - نیتریک اکسید سنتاز 2
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1861, Issue 12, Part A, December 2016, Pages 2020-2028
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1861, Issue 12, Part A, December 2016, Pages 2020-2028
نویسندگان
Mieke Poland, Jean Paul ten Klooster, Zheng Wang, Raymond Pieters, Mark Boekschoten, Renger Witkamp, Jocelijn Meijerink,