Interferon-β stabilizes barrier characteristics of the blood-brain barrier in four different species in vitro

Jörg Kraus, K. Voigt, A. M. Schuller, M. Scholz, K. S. Kim, M. Schilling, W. R. Schäbitz, P. Oschmann, B. Engelhardt

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Blood-brain barrier (BBB) breakdown is an early event in the pathogenes of multiple sclerosis (MS). In a previous study we have found a direct stabilization of barrier characteristics after treatment of bovine brain capillary endothelial cells (BCECs) with human recombinant interferon-β-1a (IFN-β-1a) in an in vitro BBB model. In the present study we examined the effect of human recombinant IFN-β-1a on the barrier properties of BCECs derived from four different species including humans to predict treatment efficacy og IFN-β-1a in MS patients. Methods: We used primary bovine and porcine BCECs, as well as human and murine EC cell lines. We investigated the influence of human recombinant IFN-β-1a on the paracellular permeability for 3H-inulin and 14C-sucrose across monolayers of bovine, human, and murine BCECs. In addition, the transendothelial electrical esistance (TEER) was determined in in vitro systems applying porcine and murine BCECS. Results: We found a stabilizing effect on the barrier characteristics of BCECs after pretreatment with IFN-β-1a in all applied in vitro models: addition of IFN-β-1a resulted in a significant decrease of the paracellular permeability across monolayers of human, bovine, and murine BCECs. Furthermore, the TEER was significantly increas, after pretreatment of porcine and murine BCECs with IFN-β-1a. Conclusion: Our data suggest that BBB stabilization by IFN-β-1a may contribute to its beneficial effects in the treatment of MS. A human in vitro BBB model might be useful as bioassay for testing the treatment efficacy of drugs in MS.

Original languageEnglish (US)
Pages (from-to)843-852
Number of pages10
JournalMultiple Sclerosis
Volume14
Issue number6
DOIs
StatePublished - Jul 2008

Keywords

  • Blood-brain barrier
  • Cell culture
  • Endothelial cells
  • Immunology
  • Interferon-β
  • Multiple sclerosis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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