J Physiol Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Physiol Volume 586, Number 7, 1937-1949, April 1, 2008 DOI: 10.1113/jphysiol.2007.146852
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
586/7/1937    most recent
jphysiol.2007.146852v1
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Förster, C.
Right arrow Articles by Drenckhahn, D.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Förster, C.
Right arrow Articles by Drenckhahn, D.
Related Collections
Right arrow Cardiovascular

CARDIOVASCULAR

Differential effects of hydrocortisone and TNF{alpha} on tight junction proteins in an in vitro model of the human blood–brain barrier

 Carola Förster1, Malgorzata Burek1, Ignacio A. Romero2, Babette Weksler3, Pierre-Olivier Couraud4 and Detlev Drenckhahn1

1 University of Würzburg, Institute of Anatomy and Cell Biology, Koellikerstrasse 6, D-97070 Würzburg, Germany
2 Immunology and Cell Biology Group, Department of Biological Sciences, Open University, Walton Hall, Milton Keynes MK7 6AA, UK
3 Weill Medical College of Cornell University, New York, NY 10021, USA
4 Institut Cochin, Centre National de la Recherche Scientifique UMR 8104, Institut National de la Santé et de la Recherche Médicale (INSERM) U567, Université René Descartes, Paris, France

Homeostasis of the central nervous system (CNS) microenvironment is maintained by the blood–brain barrier (BBB) which regulates the transport of molecules from blood into brain and back. Many disorders change the functionality and integrity of the BBB. Glucocorticoids are being used sucessfully in the treatment of some disorders while their effects on others are questionable. In addition, conflicting results between clinical and experimental experience using animal models has arisen, so that the results of molecular studies in animal models need to be revisited in an appropriate in vitro model of the human BBB for more effective treatment strategies. Using the human brain microvascular endothelial cell line hCMEC/D3, the influence of glucocorticoids on the expression of barrier constituting adherens junction and tight junction transmembrane proteins (VE-cadherin, occludin, claudins) was investigated and compared to other established BBB models. In hCMEC/D3 cells the administration of glucocorticoids induced expression of the targets occludin 2.75 ± 0.04-fold and claudin-5 up to 2.32 ± 0.11-fold, which is likely to contribute to the more than threefold enhancement of transendothelial electrical resistance reflecting barrier tightness. Our analyses further provide direct evidence that the GC hydrocortisone prevents endothelial barrier breakdown in response to pro-inflammatory stimuli (TNF{alpha} administration), which could be demonstrated to be partly based on maintenance of occludin levels. Our studies strongly suggest stabilization of BBB function as a mode of GC action on a molecular level in the human brain vasculature.

(Received 17 October 2007; accepted after revision 31 January 2008; first published online 7 February 2008)
Corresponding author C. Förster: Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstrasse 6, D-97070 Würzburg, Germany.  Email: carola.foerster{at}mail.uni-wuerzburg.de






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 The Physiological Society.