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Matrix metalloproteinase-9 and -7 are regulated in experimental autoimmune encephalomyelitis
B C Kieseier1, R Kiefer, J M Clements
1Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
Abstract:
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.
Insights
Matrix metalloproteinases (MMPs), specifically MMP-9 and MMP-7, are upregulated in the central nervous system during experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. Their increased expression correlates with disease severity and proteolytic activity.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are enzymes involved in tissue remodeling.
- Their role in inflammatory central nervous system (CNS) diseases like multiple sclerosis is not fully understood.
- Investigating MMP expression patterns in CNS inflammation is crucial.
Purpose of the Study:
- To determine the expression and activity of matrix metalloproteinases (MMPs) in the spinal cord during experimental autoimmune encephalomyelitis (AT-EAE).
- To identify specific MMPs that are upregulated during this inflammatory condition.
- To correlate MMP expression with disease severity.
Main Methods:
- Adoptive transfer experimental autoimmune encephalomyelitis (AT-EAE) model in animals.
- Semiquantitative competitive reverse transcriptase-polymerase chain reaction (RT-PCR) for mRNA analysis.
- Gelatin zymography to assess proteolytic activity.
- Immunohistochemistry to localize enzyme expression.
Main Results:
- 92-kDa gelatinase (MMP-9) mRNA levels significantly increased, peaking at maximum disease severity.
- Enhanced MMP-9 proteolytic activity was observed.
- MMP-9 immunoreactivity was detected in diseased spinal cords (meninges, blood vessels, parenchyma).
- Matrilysin (MMP-7) mRNA was also upregulated, correlating with peak disease.
- MMPs-3, -10, -11, and -13 mRNA levels remained unchanged.
Conclusions:
- 92-kDa gelatinase (MMP-9) and matrilysin (MMP-7) are selectively upregulated in the CNS during AT-EAE.
- These MMPs may play a significant role in the pathogenesis of inflammatory CNS diseases.
- Further research into MMP-9 and MMP-7 functions in neuroinflammation is warranted.