Effect of linoleic acid on endothelial cell inflammatory mediators.
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.
Young
V M
VM
Department of Nutrition and Food Science, University of Kentucky, Lexington 40506-0054, USA.
Toborek
M
M
Yang
F
F
McClain
C J
CJ
Hennig
B
B
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
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