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Published online before print June 12, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1005611

Received for publication October 26, 2005.
Revised April 8, 2006.
Accepted for publication April 10, 2006.

Article

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 ^*@

*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

^@ To whom correspondence should be addressed. E-mail: dalessio{at}vjf.inserm.fr.

	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 (TNF-) stimulation, pretreatment for 6 h with tripterine at nontoxic concentrations of 20-200 nM inhibits the expression of E-selectin, vascular 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-1 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 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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