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

J Neuroimmunol. 1997 Jul;77(1):107-15. doi: 10.1016/s0165-5728(97)00067-2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / blood supply*
  • Brain / immunology
  • Brain / metabolism
  • Brain Chemistry / immunology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / toxicity*
  • 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
  • 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

Substances

  • Carrier Proteins
  • E-Selectin
  • Interleukin-6
  • Interleukin-8
  • Membrane Proteins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Proteins
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • recombinant human tumor necrosis factor-binding protein-1