The expression of microfilament-associated cell-cell contacts in brain endothelial cells is modified by IFN-beta1a (Rebif).

In multiple sclerosis (MS), a crucial step in the induction phase of the inflammatory process in the central nervous system (CNS) is the disruption of the endothelial blood-brain barrier (BBB). Its permeability depends on the expression of intercellular adhesion molecules, such as vinculin and N-cadherin in endothelial cells. Interferon-gamma (IFN-gamma), as a proinflammatory cytokine, decreases the expression of both adhesion molecules in epithelial and astrocytic cells, whereas IFN-beta1a, an established treatment for MS, increases the expression of N-cadherin and vinculin in astrocytic cells and is postulated to preserve endothelial cell barrier function and to inhibit transendothelial migration of activated leukocytes. We analyzed the expression of N-cadherin and vinculin in a murine brain endothelial cell line by immunofluorescence staining and Western blot to study the presumed reversal effects of IFN-beta1a (Rebif, Serono Pharma, Unterschleissheim, Germany) and IFN-gamma on the formation of intercellular contacts. Vinculin and N-cadherin expression in brain endothelial cells was decreased after treatment with IFN-gamma, whereas stimulation with IFN-beta1a caused increased expression of both adhesion molecules. Combined treatment with both IFNs did not affect vinculin and N-cadherin expression. These data suggest that IFN-gamma contributes to BBB disruption by decreasing and IFN-beta1a restores the BBB by an upregulation of vinculin and N-cadherin expression in brain endothelial cells. This action of IFN-beta1a may contribute to its beneficial effects in MS therapy.