Tripterine inhibits the expression of adhesion molecules in activated endothelial cells

Journal of Leukocyte Biology

Patrizia d’Alessio⁴  Wan-zhang Qin²  Anthony Marconi⁴  Deng-hai Zhang¹  Li-min Xu⁵  Georges Uzan⁴  Guo-wu Sun⁵  Chang-quan Ling³  Xiao-ling Feng⁵  Chun-xin Yang² 

[1] INSERM U602, Hôpital Paul Brousse, Villejuif, France; Shanghai Pudong Gongli Hospital, Ruijin Hospital Group, Jiao Tong University, China; INSERM U602, Hôpital Paul Brousse, Villejuif, France; INSERM U602, Hôpital Paul Brousse, Villejuif, France; Shanghai Pudong Gongli Hospital, Ruijin Hospital Group, Jiao Tong University, China; Shanghai Pudong Gongli Hospital, Ruijin Hospital Group, Jiao Tong University, China; INSERM U602, Hôpital Paul Brousse, Villejuif, France; Shanghai Pudong Gongli Hospital, Ruijin Hospital Group, Jiao Tong University, China;;Zhongshan Hospital, Fudan University, Shanghai, China; and Zhongshan Hospital, Fudan University, Shanghai, China; and Zhongshan Hospital, Fudan University, Shanghai, China; and;Changhai Hospital, Shanghai Second Military Medical University, China Changhai Hospital, Shanghai Second Military Medical University, China Changhai Hospital, Shanghai Second Military Medical University, ChinaINSERM U602, Hôpital Paul Brousse, Villejuif, France; INSERM U602, Hôpital Paul Brousse, Villejuif, France; INSERM U602, Hôpital Paul Brousse, Villejuif, France;Shanghai Pudong Gongli Hospital, Ruijin Hospital Group, Jiao Tong University, China; Shanghai Pudong Gongli Hospital, Ruijin Hospital Group, Jiao Tong University, China; Shanghai Pudong Gongli Hospital, Ruijin Hospital Group, Jiao Tong University, China;

关键词: inflammation;    ICAM-1;    VCAM-1;    NSAID;    Chinese medicinal plant;   

DOI  :  10.1189/jlb.1005611

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown