Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothehal interactions through activation of PPARα

被引:118
作者
Sethi, S
Ziouzenkova, O
Ni, HY
Wagner, DD
Plutzky, J
Mayadas, TN
机构
[1] Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02130 USA
[2] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02130 USA
[3] Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
关键词
D O I
10.1182/blood-2002-01-0316
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Omega-3 fatty acids, which are abundant In fish oil, improve the prognosis of several chronic inflammatory diseases although the mechanism for such effects remains unclear. These fatty acids, such as eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo oxidation. We show that oxidized, but not native unoxidized, EPA significantly inhibited human neutrophil and monocyte adhesion to endothelial cells in vitro by inhibiting endothelial adhesion receptor expression. In transcriptional coactivation assays, oxidized EPA potently activated the peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor family. In vivo, oxidized, but not native, EPA markedly reduced leukocyte rolling and adhesion to venular endothelium of lipopolysaccharide (LPS)-treated mice. This occurred via a PPARalpha-dependent mechanism because oxidized EPA had no such effect in LPS-treated PPARalpha-deficient mice. Therefore, the beneficial effects of omega-3 fatty acids may be explained by a PPARalpha-mediated anti-inflammatory effect of oxidized EPA. (C) 2002 by The American Society of Hematology.
引用
收藏
页码:1340 / 1346
页数:7
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