Published online before print June 12, 2006

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(Journal of Leukocyte Biology. 2006;80:309-319.)
© 2006 by Society for Leukocyte Biology

Tripterine inhibits the expression of adhesion molecules in activated endothelial cells

Deng-hai Zhang^*,, Anthony Marconi^*, Li-min Xu, Chun-xin Yang, Guo-wu Sun, Xiao-ling Feng, Chang-quan Ling, Wan-zhang Qin, Georges Uzan^* and Patrizia d’Alessio^*,1

^* 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
Changhai Hospital, Shanghai Second Military Medical University, China

¹Correspondence: INSERM U602, Hôpital Paul Brousse, 12 avenue Paul Vaillant Couturier, 94807, Villejuif, France. E-mail: dalessio{at}vjf.inserm.fr

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 (TNF-) 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-1ß and interferon-, 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--stimulated HUVEC. Finally, tripterine inhibited TNF--driven CAM mRNA transcription and nuclear factor-B nuclear (NF-B) 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.

Key Words: inflammation • ICAM-1 • VCAM-1 • NSAID • Chinese medicinal plant

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