title: 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.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor gamma (PPARgamma) 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 PPARgamma.
  
  
  METHODS
  The human enterocyte-like cell line Caco-2 and human dendritic cells were stimulated by interleukin (IL) 1beta and lipoprotein polysaccharide, respectively, in the presence of PPARgamma agonists (troglitazone or PUFAs) or antagonist (GW9662). Five PUFAs were tested: alpha-linolenic acid (ALA), conjugated linoleic acid (CLA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and gamma-linolenic acid (GLA). Cytokine production was measured by enzyme-linked immunosorbent assay and PPARgamma, I-kappaB, 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. PPARgamma 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 mumol/L tended to increase the expression of I-kappaB. Addition of GW9662 reversed the effect of troglitazone and PUFAs at 0.1 mumol/L on IL-8 production and decreased the expression of PPARgamma. 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 PPARgamma, and the potency of the antiinflammatory effect is linked to the number of double bonds.
authors.affiliation: Gastroenterology Section, Imperial College Faculty of Medicine, Hammersmith Hospital Campus, London, United Kingdom.
authors.forename: Rachel
authors.initials: R
authors.lastname: Marion-Letellier
authors.forename: Matt
authors.initials: M
authors.lastname: Butler
authors.forename: Pierre
authors.initials: P
authors.lastname: Déchelotte
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Playford
authors.forename: Subrata
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D015153:Blotting, Western / Q000379:methods; D018938:Caco-2 Cells; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D003713:Dendritic Cells; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000502:physiology*; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D047495:PPAR gamma / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
chemical_list: D002839:Chromans; D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D052247:Nitric Oxide Synthase Type II; D000077288:Troglitazone