title: Arachidonic acid but not eicosapentaenoic acid (EPA) and oleic acid activates NF-kappaB and elevates ICAM-1 expression in Caco-2 cells.
abstract: In patients with inflammatory bowel disease (IBD), intestinal activation of the transcription factor NF-kappaB as well as intercellular adhesion molecule (ICAM)-1 expression, which is involved in recruiting leukocytes to the side of inflammation is increased. Moreover, colonic arachidonic acid (ARA) proportions are increased and oleic acid (OA) proportions are decreased. Fish oils are protective in IBD patients however, a side-by-side comparison between effects of fish oils, ARA and OA has not been made. We therefore, compared effects of eicosapentaenoic acid (EPA) versus ARA and OA on ICAM-1 expression in Caco-2 enterocytes. To validate our model we showed that dexamethasone, sulfasalazine and PPARalpha (GW7647) or PPARgamma (troglitazone) agonists significantly lowered ICAM-1 expression. ICAM-1 expression of non-stimulated and cytokine stimulated Caco-2 cells cultured for 22 days with ARA was significant higher as compared to EPA and OA. Furthermore, ARA increased NF-kappaB activation in a reporter cell-line as compared to EPA. Antibody array analysis of multiple inflammatory proteins particularly showed an increased monocyte chemotactic protein (MCP)-1 and angiogenin production and a decreased interleukin (IL)-6 and IL-10 production by ARA as compared to EPA. Our results showed that ARA but not EPA and OA activates NF-kappaB and elevates ICAM-1 expression in Caco-2 enterocytes. It suggests that replacement of ARA by EPA or OA in the colon mucosa might have beneficial effects for IBD patients. Finally, we suggest that the pro-inflammatory effects of ARA versus EPA and OA are not related to PPARgamma activation and/or eicosanoid formation.
authors.affiliation: Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. j.ramakers@hb.unimaas.nl
authors.forename: Julian D
authors.initials: JD
authors.lastname: Ramakers
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mensink
authors.forename: Gert
authors.initials: G
authors.lastname: Schaart
authors.forename: Jogchum
authors.initials: J
authors.lastname: Plat
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology*; D018938:Caco-2 Cells; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D019301:Oleic Acid / Q000494:pharmacology*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D014162:Transfection
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D047492:Peroxisome Proliferator-Activated Receptors; D010743:Phospholipids; D018799:Intercellular Adhesion Molecule-1; D016718:Arachidonic Acid; D019301:Oleic Acid; D015118:Eicosapentaenoic Acid