Brain, Vol. 123, No. 4, 698-709,
April 2000
© 2000 Oxford University Press
Dexamethasone regulation of matrix metalloproteinase expression in CNS vascular endothelium
1 Division of Biomedical Science, Sheffield Hallam University, 2 Department of Neurology, Royal Hallamshire Hospital, Sheffield, 3 Department of Clinical Ophthalmology, Institute of Ophthalmology, UCL, London and 4 Department of Neurology, Hope Hospital, Manchester, UK
Correspondence to:
Dr K. A. C. Harkness, Department of Neurology, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK
Matrix metalloproteinases (MMPs) have been implicated in the early breakdown of the blood–brain barrier in neuroinflammatory disease. Although expression of these enzymes by resident glial cells and recruited immune cells has been described, altered expression of MMPs by the CNS vascular endothelial cells may also contribute to barrier disruption. In the present study, the in vitro expression of MMP-2 and -9 as well as tissue inhibitor of metalloproteinase (TIMP)-2 by rat CNS microvascular endothelial cells has been determined and compared with that by endothelial cell lines derived from rat aorta and high endothelial venules. Primary cultures of rat brain microvascular endothelial cells as well as the rat brain (GP8/3.9) and rat retinal endothelial (JG2/1) cell lines constitutively expressed MMP-2, -9 and TIMP-2. In vitro activation of CNS endothelium with the pro-inflammatory cytokines, tumour necrosis factor-
and interleukin-1ß, resulted in selective upregulation of MMP-9 activity, whereas no significant changes were seen in MMP-2 or TIMP-2 levels at 24 h. The addition of dexamethasone partially inhibited the cytokine-induced upregulation of MMP-9. Treatment of GP8/3.9 brain endothelial cells with active MMP-9 caused subtle but distinct alterations in the expression of the junctional protein, ZO-1. Quantitative differences found between CNS and non-CNS endothelial cells in the expression of both MMP-2 and -9, and in the expression of TIMP-2 demonstrate that CNS vascular endothelium is functionally distinct from non-CNS endothelium. These results suggest that cytokine-induced upregulation of MMP-9 expression by the CNS vascular endothelium may play a role in the pathogenesis of blood–brain and blood–retinal barrier breakdown in vivo.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. E. Gralinski, S. L. Ashley, S. D. Dixon, and K. R. Spindler Mouse Adenovirus Type 1-Induced Breakdown of the Blood-Brain Barrier J. Virol., September 15, 2009; 83(18): 9398 - 9410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. N. Yan, D. D. Mruk, E. W. P. Wong, W. M. Lee, and C. Y. Cheng An autocrine axis in the testis that coordinates spermiation and blood-testis barrier restructuring during spermatogenesis PNAS, July 1, 2008; 105(26): 8950 - 8955. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zeni, E. Doepker, U. S. Topphoff, S. Huewel, T. Tenenbaum, and H.-J. Galla MMPs contribute to TNF-{alpha}-induced alteration of the blood-cerebrospinal fluid barrier in vitro Am J Physiol Cell Physiol, September 1, 2007; 293(3): C855 - C864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Svedin, H. Hagberg, K. Savman, C. Zhu, and C. Mallard Matrix Metalloproteinase-9 Gene Knock-out Protects the Immature Brain after Cerebral Hypoxia-Ischemia J. Neurosci., February 14, 2007; 27(7): 1511 - 1518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Reijerkerk, G. Kooij, S. M. A. van der Pol, S. Khazen, C. D. Dijkstra, and H. E. de Vries Diapedesis of monocytes is associated with MMP-mediated occludin disappearance in brain endothelial cells FASEB J, December 1, 2006; 20(14): 2550 - 2552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Z. Lee, B. Xu, T. Hashimoto, C. E. McCulloch, G.-Y. Yang, and W. L. Young Doxycycline Suppresses Cerebral Matrix Metalloproteinase-9 and Angiogenesis Induced by Focal Hyperstimulation of Vascular Endothelial Growth Factor in a Mouse Model Stroke, July 1, 2004; 35(7): 1715 - 1719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Cucullo, N. Marchi, M. Marroni, V. Fazio, S. Namura, and D. Janigro Blood-Brain Barrier Damage Induces Release of {alpha}2-Macroglobulin Mol. Cell. Proteomics, April 1, 2003; 2(4): 234 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hashimoto, G. Wen, M. T. Lawton, N. J. Boudreau, A. W. Bollen, G.-Y. Yang, N. M. Barbaro, R. T. Higashida, C. F. Dowd, V. V. Halbach, et al. Abnormal Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Brain Arteriovenous Malformations * Growth and Bleeding in BAVM: Another Role for MMPs Stroke, April 1, 2003; 34(4): 925 - 931. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Eberhardt, M. Schulze, C. Engels, E. Klasmeier, and J. Pfeilschifter Glucocorticoid-Mediated Suppression of Cytokine-Induced Matrix Metalloproteinase-9 Expression in Rat Mesangial Cells: Involvement of Nuclear Factor-{kappa}B and Ets Transcription Factors Mol. Endocrinol., August 1, 2002; 16(8): 1752 - 1766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Asahi, X. Wang, T. Mori, T. Sumii, J.-C. Jung, M. A. Moskowitz, M. E. Fini, and E. H. Lo Effects of Matrix Metalloproteinase-9 Gene Knock-Out on the Proteolysis of Blood-Brain Barrier and White Matter Components after Cerebral Ischemia J. Neurosci., October 1, 2001; 21(19): 7724 - 7732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Michel, R. Zobotke, M. Mader, and R. Nau Regulation of Matrix Metalloproteinase Expression in Endothelial Cells by Heat-Inactivated Streptococcus pneumoniae Infect. Immun., March 1, 2001; 69(3): 1914 - 1916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. N. Mandler, J. D. Dencoff, F. Midani, C. C. Ford, W. Ahmed, and G. A. Rosenberg Matrix metalloproteinases and tissue inhibitors of metalloproteinases in cerebrospinal fluid differ in multiple sclerosis and Devic's neuromyelitis optica Brain, March 1, 2001; 124(3): 493 - 498. [Abstract] [Full Text] [PDF]
|
|