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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 contribution
posted on 2023-05-17, 08:09 authored by Marion-Letellier, R, Butler, M, Dechelotte, P, Playford, RJ, Ghosh, S
Background: Peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ. Design: The human enterocyte-like cell line Caco-2 and human dendritic cells were stimulated by interleukin (IL) 1β and lipoprotein polysaccharide, respectively, in the presence of PPARγ agonists (troglitazone or PUFAs) or antagonist (GW9662). Five PUFAs were tested: α-linolenic acid (ALA), conjugated linoleic acid (CLA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and γ-linolenic acid (GLA). Cytokine production was measured by enzyme-linked immunosorbent assay and PPARγ, I-κB, 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. PPARγ 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 μmol/L tended to increase the expression of I-κB. Addition of GW9662 reversed the effect of troglitazone and PUFAs at 0.1 μmol/L on IL-8 production and decreased the expression of PPARγ. 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 PPARγ, and the potency of the antiinflammatory effect is linked to the number of double bonds. © 2008 American Society for Nutrition.


Publication title

American Journal of Clinical Nutrition: A Journal Reporting The Practical Application of Our World-Wide Knowledge of Nutrition










College Office - College of Health and Medicine


Amer Soc Clinical Nutrition

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9650 Rockville Pike, Subscriptions, Rm L-3300, Bethesda, USA, Md, 20814-3998

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  • Restricted

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Clinical health not elsewhere classified

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