Upregulation of ADAM-17 expression in active lesions in multiple sclerosis.
ADAM-17, a disintegrin and metalloproteinase, is the major proteinase responsible for the cleavage of membrane-bound tumour necrosis factor (TNF) as well as being an active sheddase of other cytokines, cytokine receptors, growth factors and adhesion molecules. TNF is a major proinflammatory cytokine that has been identified as having a pathogenic role in inflammatory diseases within the CNS including multiple sclerosis (MS). Here we report the cellular origin and distribution of ADAM-17 expression within clinically and neuropathologically confirmed MS and normal control white matter, assessed by immunohistochemistry, western blotting and PCR. ADAM-17 expression was associated with the blood vessel endothelium, activated macrophages/microglia and parenchymal astrocytes in MS white matter. Increased levels of ADAM-17 immunoreactivity were displayed in active lesions with evidence of recent myelin breakdown. Further studies into the functional role of ADAM-17 in the pathogenesis of MS and other inflammatory conditions are required.
Plumb
J
J
Biomedical Research Centre, Sheffield Hallam University, Howard St, Sheffield S1 1WB, UK. j.plumb@shu.ac.uk
McQuaid
S
S
Cross
A K
AK
Surr
J
J
Haddock
G
G
Bunning
R A D
RA
Woodroofe
M N
MN
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072198:ADAM17 Protein; D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000473:pathology; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D008297:Male; D017628:Microglia / Q000473:pathology; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D012333:RNA, Messenger; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human