TY  - THES
T1  - Regulation of Toll-like receptor expression by glucocorticoid-induced leucine zipper and p38 MAPK in human endothelial cells
A1  - Hirschfelder,Kerstin
Y1  - 2010/10/01
N2  - Inflammatory actions in the pathophysiology of atherosclerosis are characterized by an activation of the endothelium as well as an increased expression of Toll-like receptor (TLR) 2. Aim of this work was to decipher the roles of glucocorticoid-induced leucine zipper (GILZ) and p38 mitogen-activated protein kinase (MAPK) in endothelial TLR expression. A pronounced constitutive expression of the anti-inflammatory mediator GILZ was found in human umbilical vein endothelial cells (HUVEC), which was downregulated under inflammatory conditions. This GILZ downregulation paralleled by TLR2 upregulation was confirmed in human atherosclerotic vessels. Mechanistic examinations showed that GILZ decay led to a nuclear translocation and activation of the transcription factor NF-kB resulting in upregulation of TLR2 expression. Pharmacological inhibition of p38 MAPK as well as overexpression of dominant negative p38alpha MAPK showed a positive involvement of p38 MAPK in inflammatory TLR2 expression. This p38 MAPK-mediated action, however, was independent of GILZ. Taken together, this work provides evidence for a role of GILZ and p38 MAPK in the regulation of inflammatory TLR expression in human endothelial cells and provides insides for a better understanding of inflammatory actions in atherosclerosis. 
KW  - Arteriosklerose
KW  - Entzündung
KW  - Signaltransduktion
KW  - Toll-like-Rezeptoren
KW  - Tumor-Nekrose-Faktor
KW  - Endothel
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2010/3375
ER  -