Bacterial lipopolysaccharide and IFN-gamma induce Toll-like receptor 2 and Toll-like receptor 4 expression in human endothelial cells: role of NF-kappa B activation.
Bacterial lipopolysaccharide and IFN-gamma induce Toll-like receptor 2 and Toll-like receptor 4 expression in human endothelial cells: role of NF-kappa B activation.
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发表时间：
2001
影响因子：
4.4
通讯作者：
E. Faure;L. Thomas;H. Xu;A. Medvedev;O. Equils;M. Arditi
中科院分区：
文献类型：
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作者：
E. Faure;L. Thomas;H. Xu;A. Medvedev;O. Equils;M. Arditi
Toll样受体(TLR4)被认为是肠道内毒素的主要受体，而TLR2被认为是革兰氏阳性和真菌细胞壁成分以及细菌、分枝杆菌和螺旋体脂蛋白的受体。内毒素等微生物细胞壁成分对血管内皮细胞(EC)的激活或损伤在脓毒症和感染性休克的发生发展中起着至关重要的作用。我们以前已经证明EC主要表达TLR4，并且很少表达TLR2。这些细胞通过TLR4对内毒素反应强烈，但对脂蛋白和其他TLR2配体不反应。在这里，我们证明了内毒素、肿瘤坏死因子-α或干扰素-γ诱导人真皮微血管内皮细胞和人脐静脉内皮细胞表达TLR2。此外，内毒素和干扰素-γ协同诱导内皮细胞TLR2的表达，并且内毒素诱导的TLR2的表达依赖于NF-kappaB。脂多糖和干扰素-γ也可上调内皮细胞TLR4mRNA的表达。这些数据表明，内皮细胞中TLR2和TLR4的表达受炎症分子如内毒素、肿瘤坏死因子-α或干扰素-γ的调节。TLR2和TLR4分子可能使EC对TLR2配体产生应答，并可能有助于解释内毒素与脂蛋白、内毒素与干扰素-γ之间的协同作用，从而诱导与革兰氏阴性脓毒症相关的休克。
Toll-like receptor (TLR) 4 has been identified as the primary receptor for enteric LPS, whereas TLR2 has been implicated as the receptor for Gram-positive and fungal cell wall components and for bacterial, mycobacterial, and spirochetal lipoproteins. Vascular endothelial cell (EC) activation or injury by microbial cell wall components such as LPS is of critical importance in the development of sepsis and septic shock. We have previously shown that EC express predominantly TLR4, and have very little TLR2. These cells respond vigorously to LPS via TLR4, but are unresponsive to lipoproteins and other TLR2 ligands. Here we show that LPS, TNF-alpha, or IFN-gamma induce TLR2 expression in both human dermal microvessel EC and HUVEC. Furthermore, LPS and IFN-gamma act synergistically to induce TLR2 expression in EC, and LPS-induced TLR2 expression is NF-kappaB dependent. LPS and IFN-gamma also up-regulate TLR4 mRNA expression in EC. These data indicate that TLR2 and TLR4 expression in ECs is regulated by inflammatory molecules such as LPS, TNF-alpha, or IFN-gamma. TLR2 and TLR4 molecules may render EC responsive to TLR2 ligands and may help to explain the synergy between LPS and lipoproteins, and between LPS and IFN-gamma, in inducing shock associated with Gram-negative sepsis.