title: Upregulation of ADAM-17 expression in active lesions in multiple sclerosis.
abstract: 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.
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, Howard St, Sheffield S1 1WB, UK. j.plumb@shu.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Plumb
authors.forename: S
authors.initials: S
authors.lastname: McQuaid
authors.forename: A K
authors.initials: AK
authors.lastname: Cross
authors.forename: J
authors.initials: J
authors.lastname: Surr
authors.forename: G
authors.initials: G
authors.lastname: Haddock
authors.forename: R A D
authors.initials: RA
authors.lastname: Bunning
authors.forename: M N
authors.initials: MN
authors.lastname: Woodroofe
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human