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- α (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-κB (NF-κB), 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-κB activation compared with TNF treatment alone. In addition, preexposure to 18:2 altered TNF-mediated IκB-α signaling. Within the first 15 minutes of a 90-minute period, cytoplasmic levels of IκB-α decreased more rapidly in cells treated with 18:2+TNF compared with TNF, suggesting translocation and activation of NF-κB 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.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism