Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4
Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4
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DOI：
10.1074/jbc.m011695200
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发表时间：
2001-05-18
影响因子：
4.8
通讯作者：
Hwang, D
中科院分区：
文献类型：
--
作者：
Lee, JY;Sohn, KH;Hwang, D
我们前期的研究表明，脂多糖受体Toll样受体4(TLR4)的激活足以诱导巨噬细胞核因子KB的激活和诱导环氧合酶(COX-2)的表达，脂蛋白A部分酰化的饱和脂肪酸(SFA)对内毒素的生物学活性是必不可少的，因此，我们确定这些脂肪酸是否调节内毒素诱导的信号通路和单核/巨噬细胞(RAW 264.7)COX-2的表达。结果表明，不饱和脂肪酸(UFA)诱导核因子KB活化和COX-2等炎症标志物的表达。这种诱导被显性负TLR4抑制。不饱和脂肪酸可抑制SFA、TLR4或内毒素诱导的COX-2表达。然而，不饱和脂肪酸不能抑制TLR4下游信号成分激活所诱导的COX-2表达，这些结果表明，SFA诱导的COX-2表达和UFA对COX-2的抑制都是通过TLR4衍生的共同信号通路介导的，这些结果代表了脂肪酸调节信号通路和靶基因表达的一种新机制。此外，这些结果表明，TLR4可能通过不同类型的游离脂肪酸调节单核/巨噬细胞激活的倾向，而不同类型的膳食脂肪又可以改变TLR4的活性。
Results from our previous studies demonstrated that activation of Toll-like receptor 4 (Tlr4), the lipopolysaccharide (LPS) receptor, is sufficient to induce nuclear factor KB activation and expression of inducible cyclooxygenase (COX-2) in macrophages, Saturated fatty acids (SFAs) acylated in lipid A moiety of LPS are essential for biological activities of LPS, Thus, we determined whether these fatty acids modulate LPS-induced signaling pathways and COX-2 expression in monocyte/macrophage cells (RAW 264.7), Results show that SFAs, but not unsaturated fatty acids (UFAs), induce nuclear factor KB activation and expression of COX-2 and other inflammatory markers. This induction is inhibited by a dominant-negative Tlr4. UFAs inhibit COX-2 expression induced by SFAs, constitutively active Tlr4, or LPS. However, UFAs fail to inhibit COX-2 expression induced by activation of signaling components downstream of Tlr4, Together, these results suggest that both SFA-induced COX-2 expression and its inhibition by UFAs are mediated through a common signaling pathway derived from Tlr4, These results represent a novel mechanism by which fatty acids modulate signaling pathways and target gene expression. Furthermore, these results suggest a possibility that propensity of monocyte/macrophage activation is modulated through Tlr4 by different types of free fatty acids, which in turn can be altered by kinds of dietary fat consumed.