Differenzielle Beeinflussung endothelialer Antigene und dynamischer Endothel-Lymphozyten-Interaktionen durch Dimethylfumarat und Monomethylfumarat

The influence of dimethylfumarate and monomethylfumarate on endothelial antigen expression and dynamic lymphocyte-endothelial cell interactions

by Nora Drick
Doctoral thesis
Date of Examination:2012-07-18
Date of issue:2012-07-11
Advisor:Prof. Dr. Michael P. Schön
Referee:Prof. Dr. Katrin Schäfer
Referee:Prof. Dr. Dr. Thomas Crozier
Persistent Address: http://dx.doi.org/10.53846/goediss-1568

 

 

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Abstract

English

For years Fumaric acid esters (FAE) have been successfully used in the systemic treatment of severe psoriasis. However, their pleiotropic mode of action is not yet fully understood. To further elucidate the mode of action of FAE, the effect of dimethylfumarate (DMF) and monomethylfumarate (MMF) on human endothelial cells in vitro was investigated. As Psoriasis is associated with inflammatory lymphocytic infiltrates, it was focused on adhesion molecule expression and the interaction between endothelial cells and human peripheral blood mononuclear cells (PBMC) under conditions of shear flow. Dimethylfumarate concentration-dependently reduced the TNFα-induced expression of E-selectin (CD62E), ICAM-1 (CD54) and VCAM-1 (CD106) on human umbilical vein endothelial cells (HUVEC), both on mRNA and protein level. All three proteins are essential for the initial steps of lymphocyte recruitment to inflamed tissues. Treatment with dimethylfumarate concentrations ranging between 25
Keywords: psoriasis; endothelial cells; fumaric acid esters; lymphocytes; inflammation
Schlagwörter: Psoriasis; Endothelzellen; Fumarsäureester; Lymphozyten; Entzündung
 
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