In Vitro Modulation of Adhesion Molecules, Adhesion Phenomena, and Fluid Phase Endocytosis on Human Umbilical Vein Endothelial Cells and Brain-Derived Microvascular Endothelium by IFN-β1a

Abstract

Administration of interferon-beta (IFN-beta) in multiple sclerosis (MS) patients provides clinical benefits, although its mechanism(s) of action are not completely understood. We addressed the issue of whether concentrations of IFN-beta1a close to those reached in the serum of treated MS patients could modulate either adhesion molecules or adhesion of peripheral blood mononuclear cells (PBMC) as well as fluid phase endocytosis (FPE) in human umbilical vein endothelial cells (HUVEC) and in brain-derived microvascular endothelial cells (HBMEC). Adhesion was assessed by flow cytometry, and FPE was evaluated by peroxidase uptake. In our study, 200 U/ml IFN-beta1a induced a reduction in adhesion of PBMC to HUVEC. The information reported herein may contribute to further elucidating some of the mechanisms of action of IFN-beta on vascular endothelium.

Transcellular transport of West Nile virus-like particles across human endothelial cells depends on residues 156 and 159 of envelope protein

“…However, our data suggest that WNV can be transported across endothelial cells without viral replication. Cell type difference could be the most reasonable explanation, because several studies showed that there are differences between HBMVE cells and HUVEC in the production of growth factors, immunoregulatory factors and adhesion molecules [37-39]. HBMVE cells and HUVEC differentially respond to cytokine treatment resulting in the different cytokine production and leukocyte recruitment [40,41].…”

“…HBMVE cells and HUVEC differentially respond to cytokine treatment resulting in the different cytokine production and leukocyte recruitment [40,41]. Particularly, modulation of adhesion molecules can affect endocytosis [37]. Therefore, our data seem to reflect events that can occur in peripheral tissues having tight junction such as heart and muscles rather than in CNS.…”

Anti-inflammatory properties of Type I interferons

“…Treatment of cultured endothelial cells with IFN-␤ failed to affect VCAM-1 or ICAM-1 expression, while antagonizing IFN-␥ -induced overexpression of HLA-DR antigen. However, subsequent studies indicated that in vitro exposure to IFN-␤ does inhibit basal expression of ICAM-1 in cultures of human umbilical vein endothelial cells or human brain-derived microvascular endothelial cells (BMEC) (Defazio et al, 2001). Overexpression of ICAM-1 in cultured BMEC following exposure to TNF-␣ was also reported to be counteracted by IFN-␤ Defazio et al, 2000).…”

“…This may lead to reduced adhesion of leukocytes to endothelial lining of blood vessels and hence to attenuation of the inflammatory reaction. These mechanisms have been invoked to explain the protective action of IFN-␤ against relapsing remitting MS (Corsini et al, 1997;Defazio et al, 2001;Calabresi et al, 2001).…”

Interferon-β Is a Potent Inducer of Interferon Regulatory Factor-1/2-Dependent IP-10/CXCL10 Expression in Primary Human Endothelial Cells

“…[16, 29]]. Furthermore, it has been described to reduce leukocyte adhesion to endothelial cells in vitro [30]. In part, these pro- as well as anti-inflammatory effects in MS patients may be due to largely different concentrations of IFN-β being present at the injection site and in the brain as well as to a differential behavior of various endothelial cell types.…”