Dehydroepiandrosterone administration modulates endothelial and neutrophil adhesion molecule expression in vitro.
BACKGROUND
The steroid hormone dehydroepiandrosterone (DHEA) exerts protecting effects in the treatment of traumatic and septic complications in several animal models. This effect goes along with reduced amounts of infiltrating immune cells in organs such as lung and liver. However, the underlying mechanisms of DHEA action are still not known. Adhesion molecules are important for the extravasation of neutrophils into organs where they may exhibit detrimental effects. Therefore, we investigated the in vitro effect of DHEA on the expression pattern of adhesion molecules of human endothelial cells and neutrophils.


METHODS
Endothelial cells derived from human umbilical cord were subjected to an lipopolysaccharide (LPS) challenge. DHEA was administered in two different concentrations, 10(-5) M and 10(-8) M, as a single stimulus or in combination with LPS challenge. After two, four and 24 hours, fluorescence activated cell sorter (FACS) analysis for vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and E-selectin was performed. Neutrophils were freshly isolated from blood of 10 male healthy volunteers, stimulated the same way as endothelial cells and analyzed for surface expression of L-selectin, CD11b and CD18.


RESULTS
In the present study, we were able to demonstrate effects of DHEA on the expression of every adhesion molecule investigated. DHEA exhibits opposite effects to those seen upon LPS exposure. Furthermore, these effects are both time and concentration dependent as most DHEA specific effects could be detected in the physiological concentration of 10(-8) M.


CONCLUSIONS
Thus, we conclude that one mechanism by which DHEA may exert its protection in animal models is via the differential regulation of adhesion molecule expression.
Barkhausen
Tanja
T
Department of Trauma Surgery, Hanover Medical School, Carl-Neuberg Strasse, D-30625 Hannover, Germany. barkhausen.tanja@mh-hannover.de
Westphal
Britt-Mailin
BM
Pütz
Claudia
C
Krettek
Christian
C
van Griensven
Martijn
M
D000328:Adult; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000097:blood; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism
D015815:Cell Adhesion Molecules; D003687:Dehydroepiandrosterone