Modulation of soluble and membrane-bound TNF-induced phenotypic and functional changes of human brain microvascular endothelial cells by recombinant TNF binding protein I.
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.
Lou
J
J
Dept. of APSIC, University Medical Center, Geneva, Switzerland.
Ythier
A
A
Burger
D
D
Zheng
L
L
Juillard
P
P
Lucas
R
R
Dayer
J M
JM
Grau
G E
GE
D001921:Brain / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism; D001923:Brain Chemistry / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007957:Leukocyte Adherence Inhibition Test; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008833:Microcirculation / Q000276:immunology; D010641:Phenotype; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D002352:Carrier Proteins; D019040:E-Selectin; D015850:Interleukin-6; D016209:Interleukin-8; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C069521:recombinant human tumor necrosis factor-binding protein-1