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PubMed · 7642749

Interferon-beta downregulates interferon-gamma-induced class II MHC molecule expression and morphological changes in primary cultures of human brain microvessel endothelial cells.

H K Huynh·J Oger·K Dorovini-Zis
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Abstract

Regulation of class II MHC (Ia) antigen expression by interferons beta and gamma was studied in an in vitro model of the blood-brain barrier. Primary cultures of human brain microvessel endothelial cells were incubated with IFN-beta, gamma or a combination of the two cytokines and surface expression of class II MHC molecules was investigated with the immunogold silver staining technique and enzyme-linked immunosorbent assay. Treatment of monolayers with IFN-beta (100-6000 U/ml) failed to induce Class II MHC molecules. Co-incubation with IFN-gamma (100 U/ml), with or without pretreatment with IFN-beta, significantly inhibited the IFN-gamma-induced de novo expression in a concentration-dependent manner. Downregulation was less significant when incubation with both cytokines was preceded by 2-day treatment with IFN-gamma and was not observed in cultures incubated for an additional 4 days with IFN-gamma. Endothelial cells treated with IFN-gamma exhibited prominent morphological changes and frequent overlapping. These changes were not observed in the presence of either IFN-beta or both cytokines in the media. IFN-beta alone, or in combination with IFN-gamma, significantly inhibited the growth of endothelial cells, while only slight inhibition was observed with IFN-gamma. The results of these studies suggest that IFN-beta may function in modulating IFN-gamma-mediated immune responses in the human central nervous system at the level of the blood-brain barrier and this negative regulatory mechanism may be, at least in part, responsible for the recently reported beneficial effect of IFN-beta in relapsing-remitting multiple sclerosis.

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Cells, CulturedCerebrovascular CirculationEndothelium, VascularEnzyme-Linked Immunosorbent AssayHistocompatibility Antigens Class IIHumansImmunohistochemistryInterferon-betaInterferon-gammaMicrocirculationMicroscopy, Electron, ScanningJournal ArticleResearch Support, Non-U.S. Gov't

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H K Huynh, J Oger, K Dorovini-Zis. 1995. Interferon-beta downregulates interferon-gamma-induced class II MHC molecule expression and morphological changes in primary cultures of human brain microvessel endothelial cells.. https://doi.org/10.1016/0165-5728(95)00054-6

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