TY  - JOUR
A1  - Hartlieb, Eva
A1  - Kempf, Bettina
A1  - Partilla, Miriam
A1  - Vigh, Balázs
A1  - Spindler, Volker
A1  - Waschke, Jens
T1  - Desmoglein 2 Is Less Important than Desmoglein 3 for Keratinocyte Cohesion
JF  - PLoS ONE
N2  - Desmosomes provide intercellular adhesive strength required for integrity of epithelial and some non-epithelial tissues. Within the epidermis, the cadherin-type adhesion molecules desmoglein (Dsg) 1-4 and desmocollin (Dsc) 1-3 build the adhesive core of desmosomes. In keratinocytes, several isoforms of these proteins are co-expressed. However, the contribution of specific isoforms to overall cell cohesion is unclear. Therefore, in this study we investigated the roles of Dsg2 and Dsg3, the latter of which is known to be essential for keratinocyte adhesion based on its autoantibody-induced loss of function in the autoimmune blistering skin disease pemphigus vulgaris (PV). The pathogenic PV antibody AK23, targeting the Dsg3 adhesive domain, led to profound loss of cell cohesion in human keratinocytes as revealed by the dispase-based dissociation assays. In contrast, an antibody against Dsg2 had no effect on cell cohesion although the Dsg2 antibody was demonstrated to interfere with Dsg2 transinteraction by single molecule atomic force microscopy and was effective to reduce cell cohesion in intestinal epithelial Caco-2 cells which express Dsg2 as the only Dsg isoform. To substantiate these findings, siRNA-mediated silencing of Dsg2 or Dsg3 was performed in keratinocytes. In contrast to Dsg3-depleted cells, Dsg2 knockdown reduced cell cohesion only under conditions of increased shear. These experiments indicate that specific desmosomal cadherins contribute differently to keratinocyte cohesion and that Dsg2 compared to Dsg3 is less important in this context.
KW  - expression
KW  - inhibition
KW  - DSG2
KW  - cell adhesion
KW  - desmosomal cadherins
KW  - pemphigus vulgaris
KW  - phenotype
KW  - mice
KW  - transinteraction
KW  - reorganization
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131192
VL  - 8
IS  - 1
ER  - 
TY  - JOUR
A1  - Haarmann, Axel
A1  - Nehen, Mathias
A1  - Deiß, Annika
A1  - Buttmann, Mathias
T1  - Fumaric acid esters do not reduce inflammatory NF-\(\kappa\)B/p65 nuclear translocation, ICAM-1 expression and T-cell adhesiveness of human brain microvascular endothelial cells
JF  - International Journal of Molecular Sciences
N2  - Dimethyl fumarate (DMF) is approved for disease-modifying treatment of patients with relapsing-remitting multiple sclerosis. Animal experiments suggested that part of its therapeutic effect is due to a reduction of T-cell infiltration of the central nervous system (CNS) by uncertain mechanisms. Here we evaluated whether DMF and its primary metabolite monomethyl fumarate (MMF) modulate pro-inflammatory intracellular signaling and T-cell adhesiveness of nonimmortalized single donor human brain microvascular endothelial cells at low passages. Neither DMF nor MMF at concentrations of 10 or 50 \(\mu\)M blocked the IL-1\(\beta\)-induced nuclear translocation of NF-\(\kappa\)B/p65, whereas the higher concentration of DMF inhibited the nuclear entry of p65 in human umbilical vein endothelium cultured in parallel. DMF and MMF also did not alter the IL-1\(\beta\)-stimulated activation of p38 MAPK in brain endothelium. Furthermore, neither DMF nor MMF reduced the basal or IL-1\(\beta\)-inducible expression of ICAM-1. In accordance, both fumaric acid esters did not reduce the adhesion of activated Jurkat T cells to brain endothelium under basal or inflammatory conditions. Therefore, brain endothelial cells probably do not directly mediate a potential blocking effect of fumaric acid esters on the inflammatory infiltration of the CNS by T cells.
KW  - barrier integrity
KW  - proteins
KW  - multiple sclerosis
KW  - monomethyl fumarate
KW  - p38 mitogen-activated protein kinase
KW  - cell adhesion
KW  - NF-\(\kappa\)B
KW  - dimethyl fumarate
KW  - blood-brain barrier
KW  - endothelial cells
KW  - potent inducer
KW  - gene
KW  - drug
KW  - VCAM-1
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148295
VL  - 16
ER  -