We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Downregulation of endothelial adhesion molecules by dimethylfumarate, but not monomethylfumarate, and impairment of dynamic lymphocyte-endothelial cell interactions.
- Authors
Wallbrecht, Katrin; Drick, Nora; Hund, Anna-Carina; Schön, Michael P.
- Abstract
Although fumaric acid esters (FAE) have a decade-long firm place in the therapeutic armamentarium for psoriasis, their pleiotropic mode of action is not yet fully understood. While most previous studies have focused on the effects of FAE on leucocytes, we have addressed their activity on macro- and microvascular endothelial cells. As detected both on mRNA and protein levels, dimethylfumarate effected a profound reduction of TNFα-induced expression of E-selectin (CD62E), ICAM-1 (CD54) and VCAM-1 (CD106) on two different endothelial cell populations in a concentration-dependent manner. This reduction of several endothelial adhesion molecules was accompanied by a dramatic diminution of both rolling and firm adhesive interactions between endothelial cells and lymphocytes in a dynamic flow chamber system. Dimethylfumarate, at a concentration of 50 μ m, reduced lymphocyte rolling on endothelial cells by 85.9% ( P < 0.001 compared to untreated controls), and it diminished the number of adherent cells by 88% ( P < 0.001). In contrast, monomethylfumarate (MMF) influenced neither surface expression of adhesion molecules nor interactions between endothelial cells and lymphocytes. These observations demonstrate that endothelial cells, in addition to the known effects on leucocytes, undergo profound functional changes in response to dimethylfumarate. These changes are accompanied by severely impaired dynamic interactions with lymphocytes, which constitute the critical initial step of leucocyte recruitment to inflamed tissues in psoriasis and other TNF-related inflammatory disorders.
- Subjects
ENDOTHELIAL seeding; LYMPHOCYTES; CELL communication; FUMARATES; PSORIASIS; OLIGONUCLEOTIDES; PHYSIOLOGY
- Publication
Experimental Dermatology, 2011, Vol 20, Issue 12, p980
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/j.1600-0625.2011.01376.x