Title: Effect of linoleic acid on endothelial cell inflammatory mediators.

Authors: Young, V M; Toborek, M; Yang, F; McClain, C J; Hennig, B

Published In Metabolism, (1998 May)

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.

PubMed ID: 9591748

MeSH Terms: Cells, Cultured; DNA-Binding Proteins/drug effects; DNA-Binding Proteins/metabolism; Endothelium, Vascular/chemistry; Endothelium, Vascular/cytology*; Endothelium, Vascular/drug effects; Fatty Acids, Unsaturated/administration & dosage; Fatty Acids, Unsaturated/pharmacology; Fatty Acids/administration & dosage; Fatty Acids/pharmacology; Gene Expression/genetics; Humans; Inflammation Mediators/metabolism*; Intercellular Adhesion Molecule-1/drug effects; Intercellular Adhesion Molecule-1/genetics; Interleukin-8/metabolism; Linoleic Acids/administration & dosage; Linoleic Acids/pharmacology*; NF-kappa B/drug effects; NF-kappa B/metabolism; Oxidative Stress/drug effects; Tumor Necrosis Factor-alpha/administration & dosage; Tumor Necrosis Factor-alpha/pharmacology; Umbilical Veins/chemistry; Umbilical Veins/cytology; Umbilical Veins/drug effects