Upregulation of ADAM-17 expression in active lesions in multiple sclerosis

Mult Scler. 2006 Aug;12(4):375-85. doi: 10.1191/135248506ms1276oa.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism*
  • ADAM17 Protein
  • Aged
  • Aged, 80 and over
  • Astrocytes / pathology
  • Endothelial Cells / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Macrophages / pathology
  • Male
  • Microglia / pathology
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / immunology
  • Multiple Sclerosis, Chronic Progressive / metabolism*
  • Multiple Sclerosis, Chronic Progressive / pathology*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Multiple Sclerosis, Relapsing-Remitting / metabolism*
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • Myelin Sheath / immunology
  • Myelin Sheath / metabolism
  • Myelin Sheath / pathology
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-3 / genetics
  • Tissue Inhibitor of Metalloproteinase-3 / metabolism
  • Up-Regulation / immunology

Substances

  • RNA, Messenger
  • TIMP3 protein, human
  • Tissue Inhibitor of Metalloproteinase-3
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human