Soy phosphatidylcholine inhibited TLR4-mediated MCP-1 expression in vascular cells
Soy phosphatidylcholine inhibited TLR4-mediated MCP-1 expression in vascular cells
复制标题
DOI：
10.1016/j.atherosclerosis.2009.01.010
复制
发表时间：
2009-08-01
期刊：
影响因子：
5.3
通讯作者：
Kashiwagi, Atsunori
中科院分区：
文献类型：
--
作者：
Ishikado, Atsushi;Nishio, Yoshihiko;Kashiwagi, Atsunori
通过Toll样受体4（TLR 4）的炎症信号传导已显示促进动脉粥样硬化形成。最近的证据表明，饱和脂肪酸（SFA）诱导炎症反应，通过TLR 4途径在巨噬细胞和脂肪细胞。本研究的目的是证实大豆磷脂酰胆碱（SPC）在TLR 4介导的血管细胞炎症信号中的作用，并提出SPC作为TLR 4介导的激动剂的有效抑制剂。SFAs通过激活NF-κ B B上调MCP-1启动子活性。用siRNA敲低TLR 4可降低SFA诱导的HUVECs和大鼠VSMCs MCP-1表达，而PKC或神经酰胺信号抑制剂不能抑制MCP-1的表达。此外，我们发现SPC有效地抑制由棕榈酸酯或LPS诱导的MCP-1表达，并呈剂量依赖性。然而，SPC不抑制由细胞因子如TNF-α和IL-1 β或与TLR 4以外的TLR结合的激动剂诱导的MCPA mRNA表达。此外，SPC不影响通过鲎变形细胞裂解物的凝血活性评估的LPS活性。这些结果清楚地表明SPC特异性地抑制由TLR 4依赖性信号诱导的炎症反应。总之，我们已经证明了SFA在血管细胞中通过TLR 4-NF-κ B信号传导的炎症反应中的作用。此外，我们建议SPC可以作为一种选择性抑制剂来抑制TLR 4介导的炎症信号。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Inflammatory signaling via Toll-like receptor 4 (TLR4) has been shown to facilitate atherogenesis. Recent lines of evidence show that saturated fatty acids (SFAs) induce the inflammatory response via the TLR4 pathway in macrophages and adipocytes. The aims of this study are to confirm the role of SFAs in TLR4-mediated inflammatory signaling in vascular cells and to propose soy phosphatidylcholine (SPC) as an effective inhibitor against TLR4-mediated agonists.SFAs such as palmitate and stearate increased the expression and secretion of MCP-1 in human umbilical vein endothelial cells (HUVECs) and rat vascular smooth muscle cells (VSMCs). SFAs up-regulated the activity of MCP-1 promoter through the activation of NF-kappa B. Knockdown of TLR4 using siRNA diminished the SFA-induced MCP-1 expression in HUVECs and rat VSMCs, while PKC or ceramide signal inhibitor did not inhibit the expression. Furthermore, we found that SPC effectively inhibited the MCP-1 expression induced by palmitate or LPS in a dose-dependent manner. However, SPC did riot inhibit the mRNA expression of MCPA induced by cytokines such as TNF-alpha and IL-1 beta, or by agonists binding to TLRs other than TLR4. In addition, SPC did not affect the activity of LPS assessed by clotting activity of the Limulus amoebocyte lysate. These results clearly show that SPC specifically inhibits the inflammatory responses induced by the TLR4-dependent signal.In conclusion, we have demonstrated a role of SFAs for inflammatory response via TLR4-NF-kappa B signaling in vascular cells. Moreover, we propose that SPC can be useful as a selective inhibitor to suppress the TLR4-mediated inflammatory signaling. (C) 2009 Elsevier Ireland Ltd. All rights reserved.