This Article Full Text (PDF) All Versions of this Article: 1352458508088940v1 14/6/843    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Kraus, J Articles by Engelhardt, B Search for Related Content PubMed PubMed Citation Articles by Kraus, J Articles by Engelhardt, B Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB HISTAMINE Social Bookmarking                   What's this?

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

Department of Neurology, Paracelsus Private Medical University and Salzburger Landesklinken, Christian-Doppler-Klinik, Salzburg, Austria; Department of Neurology, University Hospital of Münster, Münster, Germany, joerg.kraus{at}salk.at

K Voigt

Research Group for Multiple Sclerosis and Neuroimmunology, Department of Neurology, Justus-Liebig University of Giessen, Giessen, Germany

AM Schuller

Department of Thoracic and Cardiovascular Surgery, Johann-Wolfgang-Goethe University of Frankfurt, Frankfurt am Main, Germany

M Scholz

Department of Trauma and Hand Surgery, Heinrich-Heine University of Duesseldorf, Duesseldorf, Germany

KS Kim

Department of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA

M Schilling

Department of Neurology, University Hospital of Münster, Münster, Germany

WR Schäbitz

Department of Neurology, University Hospital of Münster, Münster, Germany

P Oschmann

Research Group for Multiple Sclerosis and Neuroimmunology, Department of Neurology, Justus-Liebig University of Giessen, Giessen, Germany

B Engelhardt

Theodor Kocher Institute, University of Bern, Bern, Switzerland

Background

Blood–brain barrier (BBB) breakdown is an early event in the pathogenesis 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 of IFN-β-1a in MS patients.

Methods

We used primary bovine and porcine BCECs, as well as human and murine BCEC 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 resistance (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 increased 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.

Key Words: blood–brain barrier • cell culture • endothelial cells • immunology • interferon-β • multiple sclerosis

This version was published on July 1, 2008

Multiple Sclerosis, Vol. 14, No. 6, 843-852 (2008)
DOI: 10.1177/1352458508088940


CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?