Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids
Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids
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DOI：
10.1194/jlr.m200361-jlr200
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发表时间：
2003-03-01
影响因子：
6.5
通讯作者：
Hwang, DH
中科院分区：
文献类型：
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作者：
Lee, JY;Plakidas, A;Hwang, DH
食用鱼油的人类受试者在体外用脂多糖（LPS）（Toll样受体4（TLR 4）的激动剂）刺激时显示出对血液单核细胞中的环氧合酶-2（考克斯-2）表达的显著抑制。稳定转染考克斯-2启动子报告基因的鼠单核细胞系（RAW 264.7）的结果也表明，LPS诱导的考克斯-2表达优先受到鱼油中主要n-3多不饱和脂肪酸（PUFA）二十二碳六烯酸（DHA，C22：6 n-3）和二十碳五烯酸（EPA，C20：5 n-3）的抑制。此外，DHA和EPA显著抑制由合成脂肽（一种TLR 2激动剂）诱导的考克斯-2表达。这些结果与DHA和EPA优先抑制LPS或脂肽诱导的NF κ B活化相关。DHA的抑制作用靶点是TLR本身或其相关分子，而不是下游信号成分。相反，饱和脂肪酸月桂酸可增强TLR 2或TRL 4激动剂诱导的考克斯-2表达。这些结果表明，n-3 PUFA对考克斯-2表达的抑制是通过调节TLR介导的信号传导途径来介导的。因此，不同类型的膳食脂肪酸对许多慢性炎性疾病发展风险的有益或有害作用可能部分地通过调节TLR来介导。
Human subjects consuming fish oil showed a significant suppression of cyclooxygenase-2 (COX-2) expression in blood monocytes when stimulated in vitro with lipopolysaccharide (LPS), an agonist for Toll-like receptor 4 (TLR4). Results with a murine monocytic cell line (RAW 264.7) stably transfected with COX-2 promoter reporter gene also demonstrated that LPS-induced COX-2 expression was preferentially inhibited by docosahexaenoic acid (DHA, C22:6n-3) and eicosapentaenoic acid (EPA, C20:5n-3), the major n-3 polyunsaturated fatty acids (PUFAs) present in fish oil. Additionally, DHA and EPA significantly suppressed COX-2 expression induced by a synthetic lipopeptide, a TLR2 agonist. These results correlated with the preferential suppression of LPS- or lipopeptide-induced NFkappaB activation by DHA and EPA. The target of inhibition by DHA is TLR itself or its associated molecules, but not downstream signaling components. In contrast, COX-2 expression by TLR2 or TRL4 agonist was potentiated by lauric acid, a saturated fatty acid. These results demonstrate that inhibition of COX-2 expression by n-3 PUFAs is mediated through the modulation of TLR-mediated signaling pathways.jlr Thus, the beneficial or detrimental effects of different types of dietary fatty acids on the risk of the development of many chonic inflammatory diseases may be in part mediated through the modulation of TLRs.