Modulation of soluble and membrane-bound TNF-induced phenotypic and functional changes of human brain microvascular endothelial cells by recombinant TNF binding protein I

• Published in: Journal of neuroimmunology 1997-07, Vol.77 (1), p.107-115
• Main Authors: Lou, J, Ythier, A, Burger, D, Zheng, L, Juillard, P, Lucas, R, Dayer, J.-M, Grau, G.E
• Format: Article
• Language: English
• Subjects: Adhesion molecules; Brain - blood supply; Brain - immunology; Brain - metabolism; Brain Chemistry - immunology; Brain microvascular endothelial cells; Carrier Proteins - genetics; Carrier Proteins - metabolism; Carrier Proteins - toxicity; Cytoadherence; Cytotoxicity; Dose-Response Relationship, Drug; E-Selectin - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Flow Cytometry; Humans; Intercellular Adhesion Molecule-1 - metabolism; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Leukocyte Adherence Inhibition Test; Membrane Proteins - genetics; Membrane Proteins - immunology; Membrane Proteins - metabolism; Microcirculation - immunology; Phenotype; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Recombinant Proteins - pharmacology; Solubility; TNF; TNF binding protein I; Tumor Necrosis Factor Decoy Receptors; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Tumor Necrosis Factor-alpha - toxicity; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(97)00067-2

In this study, the effects of TNF binding protein I (TBP I) on TNF-induced changes of human brain microvascular endothelial cells (MVEC) were investigated. TBP I completely abolished TNF-induced IL-6 production and E-selectin induction, while it partially inhibited TNF-induced IL-8 production and up-regulation of ICAM-1 and VCAM-1. Moreover, TBP I significantly inhibited TNF-induced cytotoxicity and leukocyte adherence on human brain MVEC. The inhibitory activity of TBP I for TNF was dose-dependent and related to the time of administration after TNF stimulation. In addition, TBP I inhibited membrane-bound TNF induced activation of human brain MVEC, but the concentration required was about 10-fold higher than that for soluble TNF. These results indicate a therapeutic potential for TBP I in diseases of the central nervous system associated with TNF overproduction.