Matrix metalloproteinase-9 and -7 are regulated in experimental autoimmune encephalomyelitis.
Matrix metalloproteinases (MMPs) comprise a group of proteolytic enzymes that are implicated in the pathogenesis of inflammatory diseases of the nervous system such as multiple sclerosis. However, the exact function and expression pattern of MMPs in the inflamed nervous system are not known. In the present study we investigated the expression of 92-kDa gelatinase (MMP-9) in spinal cord from animals with adoptive transfer experimental autoimmune encephalomyelitis (AT-EAE), using a semiquantitative competitive reverse transcriptase-polymerase chain reaction assay. Increased levels of MMP-9 mRNA were found with peak values at times of maximum disease severity. Increased mRNA expression was associated with enhanced proteolytic activity of this enzyme, as demonstrated by gelatin zymography. Immunohistochemistry revealed immunoreactivity along the meninges, around blood vessels and within the parenchyma, in diseased but not in normal spinal cord. Furthermore, the expression pattern of five other MMPs was investigated. Matrilysin (MMP-7) was also found to be upregulated with maximum mRNA levels at the peak of the disease. In contrast, mRNAs for collagenase-3, 72-kDa gelatinase, and stromelysin-1 and -3 were not changed. Our findings indicate that 92-kDa gelatinase and matrilysin are selectively upregulated during AT-EAE and thus may contribute to the pathogenesis of inflammatory diseases of the CNS.
Kieseier
B C
BC
Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
Kiefer
R
R
Clements
J M
JM
Miller
K
K
Wells
G M
GM
Schweitzer
T
T
Gearing
A J
AJ
Hartung
H P
HP
D000818:Animals; D017364:Collagenases / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology*; D005260:Female; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000201:enzymology
D012333:RNA, Messenger; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9