EFFECT OF LINOLEIC-ACID ON ENDOTHELIAL-CELL INFLAMMATORY MEDIATORS

Selected lipids may influence the inflammatory cascade within the vasc ular endothelium. To test this hypothesis, endothelial cells were trea ted with linoleic acid (18:2, n - 6) for 12 hours and/or tumor necrosi s 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 b efore exposure to TNF for an additional 4 hours. Exposure to 18:2 incr eased cellular oxidative stress, activated nuclear factor-kappa B (NF- kappa B), increased interleukin-8 (IL-8) production, and elevated inte rcellular adhesion molecule-1 (ICAM-1) levels. A combined exposure to 18:2+TNF resulted in decreased NF-kappa B activation compared with TNF treatment alone. In addition, preexposure to 18:2 altered TNF-mediate d I kappa B-alpha signaling. Within the first 15 minutes of a 90-minut e period, cytoplasmic levels of I kappa B-alpha, decreased more rapidl y in cells treated with 18:2+TNF compared with TNF, suggesting translo cation and activation of NF-kappa B in cultures that were pretreated w ith 18:2 before TNF exposure. A combined exposure to 18:2+TNF had vari ous 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 trea tment with TNF alone. These data suggest that selected fatty acids suc h as 18:2 can exert proinflammatory effects and, in addition, may mark edly alter TNF-mediated inflammatory events. Copyright (C) 1998 by W.B . Saunders Company.