Paeoniflorin suppresses the expression of intercellular adhesion molecule-1 (ICAM-1) in endotoxin-treated human monocytic cells
Paeoniflorin suppresses the expression of intercellular adhesion molecule-1 (ICAM-1) in endotoxin-treated human monocytic cells
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芍药苷抑制内毒素处理的人单核细胞中细胞间粘附分子-1 (ICAM-1) 的表达
DOI：
10.1111/j.1476-5381.2011.01464.x
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发表时间：
2011-09-01
影响因子：
7.3
通讯作者：
Feng, Linyin
中科院分区：
文献类型：
--
作者：
Jin, Lei;Zhang, Li-Min;Feng, Linyin
背景与目的芍药苷（PF）对大鼠学习记忆障碍和脑缺血有改善作用，对黑质多巴胺能神经元变性有保护作用。PF的神经保护作用很可能源于其抗炎特性。已发现异常高水平的细胞间粘附分子-1（ICAM-1）与广泛的炎症和免疫应答相关。在此，我们研究了PF是否调节LPS激活的分化的人单核细胞U937细胞和TNF-α刺激的人脐静脉内皮细胞（HUVECs）中升高的ICAM-1水平。通过Western印迹分析评价蛋白质水平。用免疫荧光法检测NF-κ B的转位，EMSA法检测NF-κ B与细胞核DNA的结合，KEY-10 TSPF可抑制LPS诱导的U937细胞和TNF-α诱导的HUVECs ICAM-1表达的升高。虽然以前的报道表明PF的作用是通过激活腺苷A（1）受体介导的，但在我们的实验中，应用选择性腺苷A（1）受体拮抗剂并没有改变PF的抑制作用。为了阐明PF作用的潜在机制，我们研究了其对ICAM-1表达上游信号通路的影响。PF抑制NF-κ B通路的活化，该通路调节ICAM-1的表达。TLR 4和MAPK途径被证明不参与PF在这些cells.CONCLUSIONS AND IMPLICATIONSPF抑制ICAM-1的表达在LPS处理的U937细胞和TNF-α刺激的HUVECs通过抑制NF-κ B途径的激活。
BACKGROUND AND PURPOSEPaeoniflorin (PF) has ameliorative effects on learning and memory impairment and cerebral ischaemia in rats and has protective effects against the degeneration of dopaminergic neurons in substantia nigra. The neuroprotective effects of PF are most probably derived from its anti-inflammatory property. Abnormally high levels of intercellular adhesion molecule-1 (ICAM-1) have been found to be associated with a wide range of inflammatory and immune responses. Here we studied whether PF regulates the levels of ICAM-1 elevated in LPS-activated differentiated human monocytic U937 cells and TNF-alpha-stimulated human umbilical vein endothelial cells (HUVECs).EXPERIMENTAL APPROACHmRNA levels were evaluated by RT-PCR. Protein levels were evaluated by Western blot analysis. An immunofluorescence technique was used to estimate NF-kappa B translocation, and NF-kappa B binding to nuclear DNA was determined by EMSA.KEY RESULTSPF inhibited ICAM-1 expression elevated in LPS-induced U937 cells and TNF-alpha-stimulated HUVECs. Although previous reports showed that PF's action is mediated by activating adenosine A(1) receptors, application of a selective adenosine A(1) receptor antagonist did not change the inhibitory effect of PF in our experiments. To elucidate the underlying mechanisms of the effect of PF, we studied its effect on signalling pathways upstream of ICAM-1 expression. PF suppressed the activation of the NF-kappa B pathway, which regulates the expression of ICAM-1. The TLR4 and MAPK pathways were shown not to be involved in the effects of PF in these cells.CONCLUSIONS AND IMPLICATIONSPF inhibits ICAM-1 expression in LPS-treated U937 cells and TNF-alpha-stimulated HUVECs by suppressing the activation of the NF-kappa B pathway.