Abstract
Tumour necrosis factor (TNF) is a major immunomodulatory and proinflammatory cytokine implicated in the pathogenesis of multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE). ADAM-17 cleaves membrane-bound TNF into its soluble form. The distribution and level of ADAM-17 expression within spinal cords of Lewis rats with EAE was investigated. ADAM-17 was associated with endothelial cells in the naïve and pre-disease spinal cords. In peak disease astrocytic and inflammatory cells expressed ADAM-17. Upregulation of ADAM-17 mRNA expression was coupled with a decrease in mRNA levels of its inhibitor TIMP3 suggesting a role for ADAM-17 in EAE pathogenesis.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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ADAM Proteins
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ADAM17 Protein
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Animals
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Antigens / metabolism
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Astrocytes / metabolism
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Blotting, Western / methods
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Ectodysplasins
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / metabolism*
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Gene Expression Regulation / physiology*
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Glial Fibrillary Acidic Protein / metabolism
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Immunohistochemistry / methods
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Membrane Proteins / metabolism
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Metalloendopeptidases / genetics
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Metalloendopeptidases / metabolism*
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Microscopy, Confocal / methods
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Inbred Lew
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Spinal Cord / cytology
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Spinal Cord / metabolism*
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Time Factors
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Tissue Inhibitor of Metalloproteinase-3 / genetics
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Tissue Inhibitor of Metalloproteinase-3 / metabolism*
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von Willebrand Factor / immunology
Substances
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Antigens
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Ectodysplasins
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Glial Fibrillary Acidic Protein
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Membrane Proteins
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RNA, Messenger
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Tissue Inhibitor of Metalloproteinase-3
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Von Willebrand antigen
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von Willebrand Factor
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ADAM Proteins
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Metalloendopeptidases
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ADAM17 Protein
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Adam17 protein, rat