IFN-beta1a (Rebif) modifies the expression of microfilament-associated cell-cell contacts in C6 glioma cells.
Multiple sclerosis (MS) is a chronic inflammatory disease characterized by multifocal demyelination and axonal damage in the central nervous system (CNS). The disruption of the endothelial blood-brain barrier (BBB) with consecutive transmigration of inflammatory cells into the brain parenchyma is of critical importance in the pathogenesis of MS. The integrity of the BBB and the adjacent network of glial cells partially depends on the assembly of intercellular contacts between astrocytes. We demonstrate that recombinant interferon-gamma (rIFN-gamma), a proinflammatory cytokine critically involved in the disruption of the BBB, downregulates the expression of the cell adhesion molecules N-cadherin and vinculin in astrocytic C6 cells using Western blot and immunofluorescence microscopy. By contrast, IFN-beta1a, an established treatment for relapsing-remitting MS, increases the expression of N-cadherin and vinculin and partly inhibits the downregulation of these adhesion molecules by phytohemagglutinin (PHA)-stimulated IFN-gamma-secreting human T lymphocytes in coculture experiments. In summary, we demonstrate that IFN-beta1a modifies the assembly of N-cadherin- and vinculin-mediated intercellular contacts between astrocytic C6 cells in vitro. This effect may also contribute to the therapeutic action of IFN-beta1a in MS.
Harzheim
Michael
M
Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. neurologie@uni-bonn.de
Altenschmidt
Manuela
M
Heneka
Michael T
MT
Schröder
Rolf
R
Klockgether
Thomas
T
Schmidt
Stephan
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D001253:Astrocytes / Q000502:physiology; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018920:Coculture Techniques; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000276:immunology; D005910:Glioma / Q000473:pathology*; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016596:Vinculin / Q000378:metabolism
D000276:Adjuvants, Immunologic; D015820:Cadherins; D015815:Cell Adhesion Molecules; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D016596:Vinculin; D016899:Interferon-beta; D007371:Interferon-gamma; D000068556:Interferon beta-1a