Premium
Tripterine inhibits the expression of adhesion molecules in activated endothelial cells
Author(s) -
Zhang Denghai,
Marconi Anthony,
Xu Limin,
Yang Chunxin,
Sun Guowu,
Feng Xiaoling,
Ling Changquan,
Qin Wanzhang,
Uzan Georges,
d’Alessio Patrizia
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1005611
Subject(s) - cell adhesion molecule , cell adhesion , proinflammatory cytokine , umbilical vein , tumor necrosis factor alpha , endothelium , microbiology and biotechnology , endothelial stem cell , pharmacology , biology , cytokine , vcam 1 , chemistry , immunology , inflammation , icam 1 , biochemistry , cell , endocrinology , in vitro
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 (IC 50 )=52 nM] and ICAM‐1 (IC 50 =51 nM) and 73% of E‐selectin (IC 50 =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.