细胞粘附分子
细胞粘附
促炎细胞因子
脐静脉
肿瘤坏死因子α
内皮
细胞生物学
内皮干细胞
VCAM-1
生物
药理学
细胞因子
化学
炎症
免疫学
ICAM-1
生物化学
细胞
内分泌学
体外
作者
Denghai Zhang,Anthony Marconi,Limin Xu,Chunxin Yang,Guo-wu Sun,Xiaoling Feng,Changquan Ling,Wan-zhang Qin,Georges Uzan,Patrizia d’Alessio
摘要
Abstract Cell adhesion molecules (CAM) expressed by vascular endothelium in response to cytokine stimulation play a key role in leukocyte adhesion to endothelium during the inflammatory response. Tripterine, a chemical compound of the Chinese plant Tripterygium wilfordii Hook f, displays anti-inflammatory properties in several animal models. However, mechanisms of its action are poorly understood. In the present study, we show that in inflammatory conditions, mimicked by tumor necrosis factor α (TNF-α) stimulation, pretreatment for 6 h with tripterine at nontoxic concentrations of 20–200 nM inhibits the expression of E-selectin, vascular cell adhesion molecule (CAM)-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVEC) in a dose-dependent manner. Tripterine (200 nM) almost completely inhibits expression of VCAM-1 [50% inhibitory concentration (IC50)=52 nM] and ICAM-1 (IC50=51 nM) and 73% of E-selectin (IC50=94 nM). This inhibition effect is prominent, compared with that of dexamethasone, ibuprofen, methotrexate, or probucol, which revealed a much weaker inhibition at doses as high as 1 mM. Effects on endothelial CAM of other proinflammatory cytokines, such as interleukin-1β and interferon-γ, were also inhibited significantly by tripterine. Moreover, significant inhibition was equally observable in postincubation experiments. In addition, tripterine inhibited adhesion of human monocytes and T lymphocytes to TNF-α-stimulated HUVEC. Finally, tripterine inhibited TNF-α-driven CAM mRNA transcription and nuclear factor-κB nuclear (NF-κB) translocation. Hence, we describe a new mechanism of tripterine’s anti-inflammatory action obtained at nanomolar concentrations, owing to the negative regulation of cytokine-induced adhesion molecule expression and adhesiveness in human endothelium.
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