title: Effect of linoleic acid on endothelial cell inflammatory mediators.
abstract: Selected lipids may influence the inflammatory cascade within the vascular endothelium. To test this hypothesis, endothelial cells were treated with linoleic acid (18:2, n - 6) for 12 hours and/or tumor necrosis factor-alpha (TNF) for 4 hours. For a combined exposure to 18:2 and TNF (18:2 + TNF), cells were first preenriched with 18:2 for 8 hours before exposure to TNF for an additional 4 hours. Exposure to 18:2 increased cellular oxidative stress, activated nuclear factor-kappaB (NF-kappaB), increased interleukin-8 (IL-8) production, and elevated intercellular adhesion molecule-1 (ICAM-1) levels. A combined exposure to 18:2+ TNF resulted in decreased NF-kappaB activation compared with TNF treatment alone. In addition, preexposure to 18:2 altered TNF-mediated IkappaB-alpha signaling. Within the first 15 minutes of a 90-minute period, cytoplasmic levels of IkappaB-alpha decreased more rapidly in cells treated with 18:2 + TNF compared with TNF, suggesting translocation and activation of NF-kappaB in cultures that were pretreated with 18:2 before TNF exposure. A combined exposure to 18:2+TNF had various effects on IL-8 production and ICAM-1 levels depending on the time of exposure. For example, 18:2 + TNF treatment increased ICAM-1 levels at 12 hours but decreased ICAM-1 levels at 24 hours compared with treatment with TNF alone. These data suggest that selected fatty acids such as 18:2 can exert proinflammatory effects and, in addition, may markedly alter TNF-mediated inflammatory events.
authors.affiliation: Department of Nutrition and Food Science, University of Kentucky, Lexington 40506-0054, USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Young
authors.forename: M
authors.initials: M
authors.lastname: Toborek
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.forename: C J
authors.initials: CJ
authors.lastname: McClain
authors.forename: B
authors.initials: B
authors.lastname: Hennig
mesh_terms: D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D005227:Fatty Acids / Q000008:administration & dosage / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000235:genetics; D016209:Interleukin-8 / Q000378:metabolism; D008041:Linoleic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology; D014471:Umbilical Veins / Q000737:chemistry / Q000166:cytology / Q000187:drug effects
chemical_list: D004268:DNA-Binding Proteins; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; D016209:Interleukin-8; D008041:Linoleic Acids; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1