Abstract
SCOPE: Obese adipose tissue (AT) is infiltrated by inflammatory immune cells including IL-17A-producing-T (Th17) cells. We have previously demonstrated that adipose-derived stem cells from obese (ob-ASC), but not lean AT promote Th17 cells. Because n-3 PUFA are known to inhibit obese AT inflammation, here we tested whether they could inhibit ob-ASC-mediated IL-17A secretion. METHODS AND RESULTS: The n-3 PUFA precursor, alpha-linolenic acid (ALA), or its derivatives, eicosapentaenoic, or docosahexaenoic acid, was added to co-cultures of human ob-ASC and mononuclear cells (MNC). All three inhibited IL-17A, but not IL-1β, IL-6, nor TNFα secretion. As a control, palmitic acid (PA), a saturated fatty acid, did not inhibit IL-17A secretion. ALA also inhibited IL-17A secretion mediated by adipocytes differentiated from ob-ASC. Toll-like-receptor 4 was shown to be involved in ob-ASC-mediated-IL-17A secretion, and to be inhibited by ALA, together with Cyclo-Oxygenase-2 and Signal-Transducer-and-Activator-of-transcription-3. In addition, ALA down-regulated Intercellular-Adhesion-Molecule-1 (ICAM-1) expression in both monocytes and ASC, which resulted in decreased interactions between ob-ASC and MNC, and inhibition of IL-17A secretion. CONCLUSION: We demonstrate herein that ALA inhibits Th17 cell promotion, through decreased ICAM-1expression in both ob-ASC and monocytes. This novel mechanism may contribute to explain the beneficial effects of n-3 PUFA in IL-17A-related inflammatory pathologies.
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