Chitosan oligosaccharides inhibit TNF-α-induced VCAM-1 and ICAM-1 expression in human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways
Chitosan oligosaccharides inhibit TNF-α-induced VCAM-1 and ICAM-1 expression in human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways
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DOI：
10.1016/j.carbpol.2010.01.054
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发表时间：
2010-05-23
影响因子：
11.2
通讯作者：
Du, Yu-Guang
中科院分区：
文献类型：
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作者：
Liu, Hong-Tao;Li, Wen-Ming;Du, Yu-Guang
本研究旨在探讨壳寡糖（chitosan oligosaccharides，COS）对肿瘤坏死因子（tumor necrosis factor，TNF）-α诱导的人脐静脉内皮细胞（human umbilical vein endothelial cells，HUVECs）血管黏附分子-1（vascular adhesion molecule-1，VCAM-1）和细胞间黏附分子-1（intercellular adhesion molecule-1，ICAM-1）过度表达的抑制作用。我们发现COS在转录和翻译水平有效地抑制TNF-α诱导的VCAM-1和ICAM-1的表达。信号转导研究表明，COS阻断TNF-α诱导的NF-κ B活化、I κ B α降解以及p38 MAPK和ERK 1/2磷酸化。进一步的研究表明，p38 MAPK抑制剂（58203580）和ERK 1/2抑制剂（PD 98059）可部分抑制TNF-α诱导的HUVECs中NF-κ B B的活化，并改善VCAM-1和ICAM-1的mRNA表达。此外，COS降低TNF-α诱导的U937单核细胞与HUVECs的粘附。我们的研究结果表明，COS至少部分通过阻断p38和ERK 1/2信号通路来抑制活化的HUVECs中VCAM-1和ICAM-1的产生。(C)2010爱思唯尔有限公司版权所有。
This study aimed to investigate the inhibitive effects of chitosan oligosaccharides (COS) on tumor necrosis factor (TNF)-alpha-induced over-expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs). We found that COS effectively inhibited TNF-alpha-induced expression of VCAM-1 and ICAM-1 at the level of transcription and translation. Signal transduction studies suggested that COS blocked TNF-alpha-induced activation of NF-kappa B, degradation of I kappa B alpha, and phosphorylation of p38 MAPK and ERK1/2. A further investigation showed that the NF-kappa B activation can be partly suppressed by p38 MAPK inhibitor (58203580) and ERK1/2 inhibitor (PD98059), which also ameliorated the mRNA expression of VCAM-1 and ICAM-1 in TNF-alpha-induced HUVECs. Additionally, COS decreased U937 monocyte adhesion to HUVECs induced by TNF-alpha. Our findings suggest that COS inhibit VCAM-1 and ICAM-1 production in activated HUVECs at least partly through the blockade of p38 and ERK1/2 signaling pathways. (C) 2010 Elsevier Ltd. All rights reserved.