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Interferon‐β stabilizes barrier characteristics of brain endothelial cells in vitro
Author(s) -
Kraus Jörg,
Ling Anne K.,
Hamm Stefan,
Voigt Kay,
Oschmann Patrick,
Engelhardt Britta
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20161
Subject(s) - blood–brain barrier , tight junction , paracellular transport , in vitro , in vivo , endothelial stem cell , microbiology and biotechnology , chemistry , permeability (electromagnetism) , astrocyte , endothelium , biology , immunology , pharmacology , biophysics , biochemistry , central nervous system , endocrinology , membrane
Multiple sclerosis (MS) is accompanied by a breakdown of the blood–brain barrier (BBB) leading to edema formation and aggravation of the disease. Interferon‐β (IFN‐β) has been approved for the treatment of MS and besides its immunomodulatory effects has been demonstrated to lead to a stabilization of BBB integrity in vivo. To investigate whether human recombinant IFN‐β exerts direct effects on the BBB, we used an in vitro BBB model in which brain endothelial cells in coculture with astrocytes form a tight permeability barrier for 3 H‐inulin and 14 C‐sucrose. Removal of the astrocytes from the coculture or alternatively addition of histamine resulted in an increased paracellular permeability for small tracers across the brain endothelial cell monolayer. Strikingly, in the presence of IFN‐β, permeability increase under both conditions was inhibited. Permeability changes were accompanied by minor changes in the staining for tight junction–associated proteins in brain endothelial cell monolayers. Taken together, our data demonstrate a direct stabilizing effect of IFN‐β on BBB cerebral endothelial cells in vitro that might significantly contribute to the beneficial effects of IFN‐β treatment in MS in vivo. Ann Neurol 2004;56:192–205