Toll-like receptor 4 mediates inflammatory cytokine secretion in smooth muscle cells induced by oxidized low-density lipoprotein.
Toll-like receptor 4 mediates inflammatory cytokine secretion in smooth muscle cells induced by oxidized low-density lipoprotein.
复制标题
Toll 样受体 4 介导氧化低密度脂蛋白诱导的平滑肌细胞中炎症细胞因子的分泌。
DOI：
10.1371/journal.pone.0095935
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Yang K;Zhang XJ;Cao LJ;Liu XH;Liu ZH;Wang XQ;Chen QJ;Lu L;Shen WF;Liu Y
氧化低密度脂蛋白（oxLDL）调节平滑肌细胞（SMCs）分泌炎性细胞因子被认为是动脉粥样硬化进展的重要步骤;然而，其潜在机制尚不清楚。本研究探讨了Toll样受体4（TLR 4）在oxLDL诱导的SMC体内和体外炎症细胞因子表达中的作用。结果发现，股动脉狭窄患者动脉粥样硬化斑块中平滑肌细胞TLR 4、白细胞介素1-β（IL 1-β）、肿瘤坏死因子-α（TNFα）、单核细胞趋化蛋白1（MCP-1）和基质金属蛋白酶2（MMP-2）的表达水平升高。在野生型小鼠培养的主动脉平滑肌细胞中，oxLDL引起TLR 4和细胞因子表达水平的剂量和时间依赖性增加。这些作用在TLR 4敲除小鼠（TLR 4 −/−）的动脉SMC中显著减弱。此外，TLR 4特异性抗体可阻断原代SMC中炎性细胞因子的分泌。在TLR 4 −/−原代SMC中或用TLR 4特异性抗体处理时，Ox-LDL诱导的p38和NFκB活化也受到抑制。这些结果表明，TLR 4在oxLDL诱导的炎性细胞因子表达和分泌以及p38和NFκB活化中是一个重要的介导者。
Oxidized low-density lipoprotein (oxLDL)-regulated secretion of inflammatory cytokines in smooth muscle cells (SMCs) is regarded as an important step in the progression of atherosclerosis; however, its underlying mechanism remains unclear. This study investigated the role of toll-like receptor 4 (TLR4) in oxLDL-induced expression of inflammatory cytokines in SMCs both in vivo and in vitro. We found that the levels of TLR4, interleukin 1-β (IL1-β), tumor necrosis factor-α (TNFα), monocyte chemoattractant protein 1 (MCP-1) and matrix metalloproteinase-2 (MMP-2) expression were increased in the SMCs of atherosclerotic plaques in patients with femoral artery stenosis. In cultured primary arterial SMCs from wild type mice, oxLDL caused dose- and time-dependent increase in the expression levels of TLR4 and cytokines. These effects were significantly weakened in arterial SMCs derived from TLR4 knockout mice (TLR4−/−). Moreover, the secretion of inflammatory cytokines was blocked by TLR4-specific antibodies in primary SMCs. Ox-LDL induced activation of p38 and NFκB was also inhibited in TLR4−/− primary SMCs or when treated with TLR4-specific antibodies. These results demonstrated that TLR4 is a crucial mediator in oxLDL-induced inflammatory cytokine expression and secretion, and p38 and NFκB activation.
登录
查看更多内容
影响因子：
--
作者：
Ji, Yuanyuan;Liu, Juntian;Liu, Na
通讯作者：
Liu, Na
DOI：
10.1161/01.atv.0000218496.60097.e0
发表时间：
2006-05-01
影响因子：
8.7
作者：
Kuzuya, M;Nakamura, K;Iguchi, A
通讯作者：
Iguchi, A
影响因子：
5.6
作者：
Falck-Hansen M;Kassiteridi C;Monaco C
通讯作者：
Monaco C
DOI：
10.1073/pnas.0403249101
发表时间：
2004-07-20
影响因子：
11.1
作者：
Michelsen, KS;Wong, MH;Arditi, M
通讯作者：
Arditi, M
影响因子：
4.8
作者：
Hsu, HY;Twu, YC
通讯作者：
Twu, YC