Abstract
ADAM-17 expression is localised to endothelial cells in the human central nervous system (CNS) and is increased in multiple sclerosis (MS) white matter, suggesting a role in MS pathogenesis. Expression of ADAM-17, TIMP-3, and fractalkine were investigated in a human brain endothelial cell line (hCMEC/D3) after pro-inflammatory cytokine treatment. Tumour necrosis factor (TNF) significantly increased fractalkine mRNA (>100 fold) and protein expression, which was associated with increased shedding of fractalkine from the cell. Fractalkine shedding may regulate immune cell trafficking into the CNS, however, this does not appear to be directly controlled by ADAM-17 activity.
MeSH terms
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ADAM Proteins / genetics
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ADAM Proteins / metabolism*
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ADAM17 Protein
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Cell Line
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Chemokine CX3CL1 / genetics
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Chemokine CX3CL1 / metabolism*
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Chemotaxis, Leukocyte / immunology
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Cytokines / metabolism*
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Cytokines / pharmacology*
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Encephalitis / immunology
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Encephalitis / metabolism
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Encephalitis / physiopathology
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Endothelial Cells / drug effects
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Endothelial Cells / immunology
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Endothelial Cells / metabolism*
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Gene Expression / drug effects
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Gene Expression / physiology
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Humans
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RNA, Messenger / analysis
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Tissue Inhibitor of Metalloproteinase-3 / genetics
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Tissue Inhibitor of Metalloproteinase-3 / metabolism
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Necrosis Factor-alpha / pharmacology
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Up-Regulation / drug effects
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Up-Regulation / immunology
Substances
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CX3CL1 protein, human
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Chemokine CX3CL1
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Cytokines
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RNA, Messenger
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Tissue Inhibitor of Metalloproteinase-3
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Tumor Necrosis Factor-alpha
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ADAM Proteins
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ADAM17 Protein
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ADAM17 protein, human