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Comparison of cytokine modulation by natural peroxisome proliferator-activated receptor gamma ligands with synthetic ligands in intestinal-like Caco-2 cells and human dendritic cells-potential for dietary modulation of peroxisome proliferator-activated receptor gamma in intestinal inflammation
journal contributionposted on 2023-05-17, 08:09 authored by Marion-Letellier, R, Butler, M, Dechelotte, P, Playford, RJ, Ghosh, S
Background: Peroxisome proliferator-activated receptor Î³ (PPARÎ³) plays a role in the regulation of intestinal inflammation and is activated by both natural (polyunsaturated fatty acid; PUFAs) and synthetic (troglitazone) ligands. The fatty acid content of defined formula diets may play a role in mediating the antiinflammatory effect, but the mechanism is unclear. Objective: We evaluated to what extent the effect of PUFAs on intestinal inflammation is mediated via PPARÎ³. Design: The human enterocyte-like cell line Caco-2 and human dendritic cells were stimulated by interleukin (IL) 1Î² and lipoprotein polysaccharide, respectively, in the presence of PPARÎ³ agonists (troglitazone or PUFAs) or antagonist (GW9662). Five PUFAs were tested: Î±-linolenic acid (ALA), conjugated linoleic acid (CLA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and Î³-linolenic acid (GLA). Cytokine production was measured by enzyme-linked immunosorbent assay and PPARÎ³, I-ÎºB, and inducible nitric oxide synthase (iNOS) expression by Western blot. Results: In Caco-2 cells, IL-6 secretion was significantly decreased by troglitazone, DHA, EPA, and GLA. IL-8 production was significantly decreased by troglitazone, ALA, DHA, EPA, and GLA. PPARÎ³ expression was significantly increased by troglitazone, DHA, and EPA. iNOS expression was significantly decreased by troglitazone, DHA, and EPA. Troglitazone and PUFAs at 0.1 Î¼mol/L tended to increase the expression of I-ÎºB. Addition of GW9662 reversed the effect of troglitazone and PUFAs at 0.1 Î¼mol/L on IL-8 production and decreased the expression of PPARÎ³. EPA and DHA also modulated the dendritic cell response to lipoprotein polysaccharide. Conclusions: The tested PUFAs exerted an antiinflammatory effect in vitro in both models. This effect of PUFAs in Caco-2 cells is similar to that of troglitazone on intestinal inflammation mediated by PPARÎ³, and the potency of the antiinflammatory effect is linked to the number of double bonds. Â© 2008 American Society for Nutrition.
Publication titleAmerican Journal of Clinical Nutrition: A Journal Reporting The Practical Application of Our World-Wide Knowledge of Nutrition
Department/SchoolCollege Office - College of Health and Medicine
PublisherAmer Soc Clinical Nutrition
Place of publication9650 Rockville Pike, Subscriptions, Rm L-3300, Bethesda, USA, Md, 20814-3998