Scientific article

Interferon-beta inhibits activated leukocyte migration through human brain microvascular endothelial cell monolayer

Published inLaboratory investigation, vol. 79, no. 8, p. 1015-1025
Publication date1999

Perivascular leukocyte infiltration into the central nervous system is characteristic of multiple sclerosis (MS) pathology. Interferon-beta (IFN-beta) has shown efficacy in the treatment of patients with MS, but the relevant mechanisms remain incompletely understood. In this study the effects of IFN-beta on leukocyte transendothelial migration were investigated using cells relevant to MS pathogenesis, namely human brain microvascular endothelial cells (HB-MVEC). Activated, but not resting leukocytes exhibited a high transendothelial migration capacity. HB-MVEC prestimulated with tumor necrosis factor (TNF) and IFN-gamma significantly promoted leukocyte transendothelial migration. IFN-beta inhibited the activated leukocyte transendothelial migration on TNF/IFN-gamma-activated HB-MVEC in a dose-dependent manner. A matrix metalloproteinase (MMP) inhibitor and monoclonal antibodies to lymphocyte function antigen-1 (LFA-1) or intercellular adhesion molecule-1 (ICAM-1), but not to very late antigen-4 or to vascular cell adhesion molecule-1 significantly inhibited the transendothelial migration of stimulated leukocytes, suggesting that this phenomenon involves the LFA-1/ICAM-1 interaction and MMP. However IFN-beta did not interfere with the binding of leukocytes to HB-MVEC unless IFN-beta was preincubated with leukocytes or added to HB-MVEC at the time of stimulation. Furthermore IFN-beta did not modulate the expression of adhesion molecules on either stimulated leukocytes or activated HB-MVEC, but partially reduced TNF and interleukin-1 production from stimulated leukocytes during coculture with HB-MVEC. Interestingly, in the presence of IFN-beta, a significant down-regulation of MMP-9 release from stimulated leukocytes was found, especially for the activated form of MMP-9. These results indicate that inhibition of leukocyte transendothelial migration is an important mechanism accounting for the beneficial effects of IFN-beta in the treatment MS patients.

  • Brain/blood supply
  • Cell Adhesion/drug effects
  • Cell Movement/drug effects
  • Cells, Cultured
  • Endothelium, Vascular/cytology
  • Humans
  • Integrin alpha4beta1
  • Integrins/physiology
  • Intercellular Adhesion Molecule-1/physiology
  • Interferon-beta/pharmacology
  • Interferon-gamma/pharmacology
  • Interleukin-1/secretion
  • Leukocytes/drug effects/physiology
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase Inhibitors
  • Microcirculation/cytology
  • Multiple Sclerosis/etiology/therapy
  • Receptors, Lymphocyte Homing/physiology
  • Tumor Necrosis Factor-alpha/secretion
  • Vascular Cell Adhesion Molecule-1/physiology
Citation (ISO format)
LOU, Jinning et al. Interferon-beta inhibits activated leukocyte migration through human brain microvascular endothelial cell monolayer. In: Laboratory investigation, 1999, vol. 79, n° 8, p. 1015–1025.
Main files (1)
Article (Published version)
ISSN of the journal0023-6837

Technical informations

Creation05/28/2015 12:11:00 PM
First validation05/28/2015 12:11:00 PM
Update time03/14/2023 11:19:39 PM
Status update03/14/2023 11:19:38 PM
Last indexation10/18/2023 11:02:07 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack