title: Tripterine inhibits the expression of adhesion molecules in activated endothelial cells.
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 alpha (TNF-alpha) 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-1beta and interferon-gamma, 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-alpha-stimulated HUVEC. Finally, tripterine inhibited TNF-alpha-driven CAM mRNA transcription and nuclear factor-kappaB nuclear (NF-kappaB) 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.
authors.affiliation: INSERM U602, Hôpital Paul Brousse, 12 avenue Paul Vaillant Couturier, 94807, Villejuif, France.
authors.forename: Deng-hai
authors.initials: DH
authors.lastname: Zhang
authors.forename: Anthony
authors.initials: A
authors.lastname: Marconi
authors.forename: Li-min
authors.initials: LM
authors.lastname: Xu
authors.forename: Chun-xin
authors.initials: CX
authors.lastname: Yang
authors.forename: Guo-wu
authors.initials: GW
authors.lastname: Sun
authors.forename: Xiao-ling
authors.initials: XL
authors.lastname: Feng
authors.forename: Chang-quan
authors.initials: CQ
authors.lastname: Ling
authors.forename: Wan-zhang
authors.initials: WZ
authors.lastname: Qin
authors.forename: Georges
authors.initials: G
authors.lastname: Uzan
authors.forename: Patrizia
authors.initials: P
authors.lastname: d'Alessio
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008958:Models, Molecular; D016328:NF-kappa B / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; C050414:celastrol