Downregulation of endothelial adhesion molecules by dimethylfumarate, but not monomethylfumarate, and impairment of dynamic lymphocyte-endothelial cell interactions

摘要: 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 focused on effects FAE leucocytes, we addressed activity macro- and microvascular endothelial cells. As detected both mRNA protein levels, dimethylfumarate effected profound reduction TNFα-induced expression E-selectin (CD62E), ICAM-1 (CD54) VCAM-1 (CD106) two different cell populations concentration-dependent manner. This several adhesion molecules was accompanied by dramatic diminution rolling adhesive interactions between cells lymphocytes dynamic flow chamber system. Dimethylfumarate, at concentration 50 μm, reduced lymphocyte 85.9% (P<0.001 compared to untreated controls), it diminished number adherent 88% (P<0.001). In contrast, monomethylfumarate (MMF) influenced neither surface nor lymphocytes. These observations demonstrate that cells, addition known undergo functional changes response dimethylfumarate. are severely impaired with lymphocytes, which constitute critical initial step leucocyte recruitment inflamed tissues psoriasis other TNF-related inflammatory disorders.