Brain, Vol 121, Issue 12 2327-2334, Copyright © 1998 by Oxford University Press
D Leppert, J Ford, G Stabler, C Grygar, C Lienert, S Huber, KM Miller, SL Hauser and L Kappos
Matrix metalloproteinases (MMPs) are a family of endopeptidases capable of
enzymatic digestion of subendothelial basement membrane and other
components of the extracellular matrix. Expression of MMP-2, -3, -7 and -9
is increased around multiple sclerosis plaques and in brain tissue in
experimental allergic encephalomyelitis. To measure quantitatively the
expression of these MMPs and their endogenous inhibitors (TIMP-1 and -2),
we analysed samples from 52 patients with relapsing-remitting and primary
progressive multiple sclerosis by ELISA (enzyme-linked immunosorbent assay)
and substrate-gel electrophoresis (zymography). MMP-9 was increased over
controls in 100% of relapsing-remitting multiple sclerosis cases, with
similar levels detected in relapses and clinically stable phases of
disease. In primary progressive multiple sclerosis, MMP-9 was increased in
57% of CSF samples, but concentrations were below those encountered in the
relapsing-remitting form. The selective upregulation of MMP-9 suggests that
T-cells and macrophages invading the brain parenchyma and the CSF space are
the predominant source of MMP-9 in multiple sclerosis. TIMPs and other MMPs
(MMP-2 and -3) were not upregulated or not detectable (MMP-7) in CSF of
patients with relapsing-remitting and primary progressive multiple
sclerosis. The sustained increase of MMP-9 in clinically stable multiple
sclerosis supports the concept that multiple sclerosis is associated with
ongoing proteolysis that may result in progressive tissue damage. The
selective inhibition of MMP-9 could be a useful approach for the prevention
of disease progression in multiple sclerosis.
ARTICLES
Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis
Department of Research, University Hospitals, Basel, Switzerland.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F Bernal, B Elias, H. Hartung, and B. Kieseier Regulation of matrix metalloproteinases and their inhibitors by interferon-{beta}: a longitudinal study in multiple sclerosis patients Multiple Sclerosis, June 1, 2009; 15(6): 721 - 727. [Abstract] [PDF]
|
|
|
|
|
|
E Fainardi, M Castellazzi, C Tamborino, A Trentini, M. Manfrinato, E Baldi, M. Tola, F Dallocchio, E Granieri, and T Bellini Potential relevance of cerebrospinal fluid and serum levels and intrathecal synthesis of active matrix metalloproteinase-2 (MMP-2) as markers of disease remission in patients with multiple sclerosis Multiple Sclerosis, May 1, 2009; 15(5): 547 - 554. [Abstract] [PDF]
|
|
|
|
|
|
Y Benesova, A Vasku, H Novotna, J Litzman, P Stourac, M Beranek, Z Kadanka, and J Bednarik Matrix metalloproteinase-9 and matrix metalloproteinase-2 as biomarkers of various courses in multiple sclerosis Multiple Sclerosis, March 1, 2009; 15(3): 316 - 322. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Braitch, R. Nunan, G. Niepel, L. J. Edwards, and C. S. Constantinescu Increased Osteopontin Levels in the Cerebrospinal Fluid of Patients With Multiple Sclerosis Arch Neurol, May 1, 2008; 65(5): 633 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-C. Tsai, L.-Y. Chung, E.-R. Chen, Y.-C. Liu, S. S.-J. Lee, Y.-S. Chen, C.-L. Sy, S.-R. Wann, and C.-M. Yen Association of Matrix Metalloproteinase-9 and Tissue Inhibitors of Metalloproteinase-4 in Cerebrospinal Fluid with Blood-Brain Barrier Dysfunction in Patients with Eosinophilic Meningitis Caused by Angiostrongylus cantonensis Am J Trop Med Hyg, January 1, 2008; 78(1): 20 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Schreibelt, R. J. P. Musters, A. Reijerkerk, L. R. de Groot, S. M. A. van der Pol, E. M. L. Hendrikx, E. D. Dopp, C. D. Dijkstra, B. Drukarch, and H. E. de Vries Lipoic Acid Affects Cellular Migration into the Central Nervous System and Stabilizes Blood-Brain Barrier Integrity J. Immunol., August 15, 2006; 177(4): 2630 - 2637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E Fainardi, M Castellazzi, T Bellini, M C Manfrinato, E Baldi, I Casetta, E Paolino, E Granieri, and F Dallocchio Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis Multiple Sclerosis, June 1, 2006; 12(3): 294 - 301. [Abstract] [PDF]
|
|
|
|
|
|
R P Lisak, J A Benjamins, B Bealmear, B Yao, S Land, L Nedelkoska, and D Skundric Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for immune-related molecules by central nervous system mixed glial cell cultures Multiple Sclerosis, April 1, 2006; 12(2): 149 - 168. [Abstract] [PDF]
|
|
|
|
 |
|
 T Kanesaka, M Mori, T Hattori, T Oki, and S Kuwabara Serum matrix metalloproteinase-3 levels correlate with disease activity in relapsing-remitting multiple sclerosis J. Neurol. Neurosurg. Psychiatry, February 1, 2006; 77(2): 185 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Avolio, M Filippi, C Tortorella, M A Rocca, M Ruggieri, F Agosta, V Tomassini, C Pozzilli, S Stecchi, P Giaquinto, et al. Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment Multiple Sclerosis, August 1, 2005; 11(4): 441 - 446. [Abstract] [PDF]
|
|
|
|
|
|
V Yadav, G Marracci, J Lovera, W Woodward, K Bogardus, W Marquardt, L Shinto, C Morris, and D Bourdette Lipoic acid in multiple sclerosis: a pilot study Multiple Sclerosis, April 1, 2005; 11(2): 159 - 165. [Abstract] [PDF]
|
|
|
|
|
|
J Sastre-Garriga, M Comabella, L Brieva, A Rovira, M Tintore, and X Montalban Decreased MMP-9 production in primary progressive multiple sclerosis patients Multiple Sclerosis, August 1, 2004; 10(4): 376 - 380. [Abstract] [PDF]
|
|
|
|
|
|
G. M. Liuzzi, T. Latronico, A. Fasano, G. Carlone, and P. Riccio Interferon-beta inhibits the expression of metalloproteinases in rat glial cell cultures: implications for multiple sclerosis pathogenesis and treatment Multiple Sclerosis, June 1, 2004; 10(3): 290 - 297. [Abstract] [PDF]
|
|
|
|
 |
|
 F. Gilli, A. Bertolotto, A. Sala, F. Hoffmann, M. Capobianco, S. Malucchi, T. Glass, L. Kappos, R. L.P. Lindberg, and D. Leppert Neutralizing antibodies against IFN-{beta} in multiple sclerosis: antagonization of IFN-{beta} mediated suppression of MMPs Brain, February 1, 2004; 127(2): 259 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Waubant, D. Goodkin, A. Bostrom, P. Bacchetti, J. Hietpas, R. Lindberg, and D. Leppert IFN{beta} lowers MMP-9/TIMP-1 ratio, which predicts new enhancing lesions in patients with SPMS Neurology, January 14, 2003; 60(1): 52 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Rosenberg Matrix Metalloproteinases and Neuroinflammation in Multiple Sclerosis Neuroscientist, December 1, 2002; 8(6): 586 - 595. [Abstract] [PDF]
|
|
|
|
|
|
O. Neuhaus, S. Strasser-Fuchs, F. Fazekas, B.C. Kieseier, G. Niederwieser, H.P. Hartung, and J.J. Archelos Statins as immunomodulators: Comparison with interferon-{beta}1b in MS Neurology, October 8, 2002; 59(7): 990 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G M Liuzzi, M Trojano, M Fanelli, C Avolio, A Fasano, P Livrea, and P Riccio Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple sclerosis: implication for pathogenesis Multiple Sclerosis, June 1, 2002; 8(3): 222 - 228. [Abstract] [PDF]
|
|
|
|
|
|
V. Brundula, N. B. Rewcastle, L. M. Metz, C. C. Bernard, and V. W. Yong Targeting leukocyte MMPs and transmigration: Minocycline as a potential therapy for multiple sclerosis Brain, June 1, 2002; 125(6): 1297 - 1308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. D'Souza, B. Mak, and M. A. Moscarello The Up-regulation of Stromelysin-1 (MMP-3) in a Spontaneously Demyelinating Transgenic Mouse Precedes Onset of Disease J. Biol. Chem., April 12, 2002; 277(16): 13589 - 13596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Gveric, R. Hanemaaijer, J. Newcombe, N. A. van Lent, C. F. M. Sier, and M. L. Cuzner Plasminogen activators in multiple sclerosis lesions: Implications for the inflammatory response and axonal damage Brain, October 1, 2001; 124(10): 1978 - 1988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. P. Lindberg, C. J. A. De Groot, L. Montagne, P. Freitag, P. van der Valk, L. Kappos, and D. Leppert The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis Brain, September 1, 2001; 124(9): 1743 - 1753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Han, Y. Sun, S. Scott, and D. Bleich Tissue Inhibitor of Metalloproteinase-1 Prevents Cytokine-Mediated Dysfunction and Cytotoxicity in Pancreatic Islets and {beta}-cells Diabetes, May 1, 2001; 50(5): 1047 - 1055. [Abstract] [Full Text]
|
|
|
|
|
|
N. M. Price, J. Farrar, T. T. H. Chau, N. T. H. Mai, T. T. Hien, and J. S. Friedland Identification of a Matrix-Degrading Phenotype in Human Tuberculosis In Vitro and In Vivo J. Immunol., March 15, 2001; 166(6): 4223 - 4230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Waubant, D. E. Goodkin, L. Gee, P. Bacchetti, R. Sloan, T. Stewart, P.-B. Andersson, G. Stabler, and K. Miller Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis Neurology, October 22, 1999; 53(7): 1397 - 1397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Trojano, C. Avolio, G. M. Liuzzi, M. Ruggieri, G. Defazio, M. Liguori, M. P. Santacroce, D. Paolicelli, F. Giuliani, P. Riccio, et al. Changes of serum sICAM-1 and MMP-9 induced by rIFN{beta}-1b treatment in relapsing-remitting MS Neurology, October 22, 1999; 53(7): 1402 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Kieseier, T. Seifert, G. Giovannoni, and H.-P. Hartung Matrix metalloproteinases in inflammatory demyelination: Targets for treatment Neurology, July 1, 1999; 53(1): 20 - 20. [Abstract] [Full Text]
|
|
|
|
|
|
S. J. Kridel, E. Chen, L. P. Kotra, E. W. Howard, S. Mobashery, and J. W. Smith Substrate Hydrolysis by Matrix Metalloproteinase-9* J. Biol. Chem., June 1, 2001; 276(23): 20572 - 20578. [Abstract] [Full Text] [PDF]
|
|