التفاصيل البيبلوغرافية
| العنوان: |
Dual action by fumaric acid esters synergistically reduces adhesion to human endothelium. |
| المؤلفون: |
Breuer, Johanna, Herich, Sebastian, Schneider-Hohendorf, Tilman, Chasan, Achmet I., Wettschureck, Nina, Gross, Catharina C., Loser, Karin, Zarbock, Alexander, Roth, Johannes, Klotz, Luisa, Wiendl, Heinz, Schwab, Nicholas |
| المصدر: |
Multiple Sclerosis Journal; Dec2018, Vol. 24 Issue 14, p1871-1882, 12p, 1 Color Photograph, 1 Chart, 3 Graphs |
| مصطلحات موضوعية: |
MULTIPLE sclerosis, BLOOD-brain barrier, FUMARATES, VASCULAR cell adhesion molecule-1, G protein coupled receptors |
| مستخلص: |
Objective: Dimethyl fumarate (DMF) is prescribed against relapsing-remitting multiple sclerosis (MS). Here, we investigated the effects of DMF and monomethyl fumarate (MMF), its metabolite in vivo, at the (inflamed) blood–brain barrier (BBB). Methods: Effects of fumaric acid esters were analyzed using primary human brain–derived microvascular endothelial cells (HBMECs) in combination with peripheral blood mononuclear cells (PBMCs) derived from DMF-treated MS patients. Results: MMF-binding to brain endothelium cells leads to activation of nuclear factor (erythroid-derived 2)–related factor 2 (Nrf2)–induced downregulation of vascular cell adhesion molecule 1 (VCAM-1). This might be mediated via the G-protein-coupled receptor (GPCR) hydroxycarboxylic acid receptor 2 (HCA2), a known molecular target of MMF, as we could demonstrate its expression and regulation on HBMECs. DMF treatment in vivo led to a strongly reduced expression of VCAM-1's ligand very late antigen 4 (VLA-4) by selectively reducing integrin high-expressing memory T cells of MS patients, potentially due to inhibition of their maturation by reduced trans-localization of NFκB. Conclusion: DMF-mediated VCAM-1 downregulation on the endothelial side and reduction in T cells with a migratory phenotype on the lymphocyte side result in a synergistic reduction in T-cell adhesion to activated endothelium and, therefore, to reduced BBB transmigration in the setting of MS. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
