MATRIX METALLOPROTEINASE-9 AND METALLOPROTEINASE-7 ARE REGULATED IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Matrix metalloproteinases (MMPs) comprise a group of proteolytic enzym es that are implicated in the pathogenesis of inflammatory diseases of the nervous system such as multiple sclerosis. However; the exact fun ction and expression pattern of MMPs in the inflamed nervous system ar e not known. In the present study we investigated the expression of 92 -kDa gelatinase (MMP-9) in spinal cord from animals with adoptive tran sfer experimental autoimmune encephalo myelitis (AT-EAE), using a semi quantitative competitive reverse transcriptase-polymerase chain reacti on assay. Increased level's of MMP-9 mRNA were found with peak values at times of maximum disease severity. Increased mRNA expression was as sociated with enhanced proteolytic activity of this enzyme, as demonst rated by gelatin zymography. Immunohistochemistry revealed immunoreact ivity along the meninges, around blood vessels and within the parenchy ma, in diseased bur not in normal spinal cord. Furthermore, the expres sion pattern of five other MMPs was investigated. Matrilysin (MMP-7) w as also found to be upregulated with maximum mRNA levels at the peak o f the disease. In contrast, mRNAs for collagenase-3, 72-kDa gelatinase , and stromelysin-1 and -3 were not changed. Our findings indicate tha t 92-kDa gelatinase and matrilysin are selectively upregulated during AT-EAE and thus may contribute to the pathogenesis of inflammatory dis eases of the CNS.