Interferon-beta stabilizes barrier characteristics of brain endothelial cells in vitro.
Multiple sclerosis (MS) is accompanied by a breakdown of the blood-brain barrier (BBB) leading to edema formation and aggravation of the disease. Interferon-beta (IFN-beta) 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-beta 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 3H-inulin and 14C-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-beta, 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-beta on BBB cerebral endothelial cells in vitro that might significantly contribute to the beneficial effects of IFN-beta treatment in MS in vivo.
Max-Planck Institute for Physiological and Clinical Research, Department of Vascular Cell Biology, Bad Nauheim, Germany. joerg.kraus@ukmuenster.de
Jörg
J
Kraus
Anne K
AK
Ling
Stefan
S
Hamm
Kay
K
Voigt
Patrick
P
Oschmann
Britta
B
Engelhardt
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000166:cytology*; D002199:Capillary Permeability / Q000187:drug effects; D002247:Carbon Isotopes / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D062465:Claudin-3; D018920:Coculture Techniques / Q000379:methods; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D005455:Fluorescent Antibody Technique / Q000379:methods; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007444:Inulin / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013395:Sucrose / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism; D014316:Tritium / Q000378:metabolism; D062826:Zonula Occludens-1 Protein; D014841:von Willebrand Factor / Q000276:immunology
D000941:Antigens; C568122:CLDN3 protein, human; D002247:Carbon Isotopes; D062465:Claudin-3; C568124:Cldn3 protein, rat; D008565:Membrane Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; C569042:TJP1 protein, human; C569044:Tjp1 protein, rat; C029417:Von Willebrand antigen; D062826:Zonula Occludens-1 Protein; D014841:von Willebrand Factor; D014316:Tritium; D013395:Sucrose; D016899:Interferon-beta; D006632:Histamine; D007444:Inulin