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

J Plumb1, S McQuaid, A K Cross

  • 1Biomedical Research Centre, Sheffield Hallam University, Howard St, Sheffield S1 1WB, UK. j.plumb@shu.ac.uk

Multiple Sclerosis (Houndmills, Basingstoke, England)
|August 12, 2006
PubMed

Insights

ADAM-17, an enzyme linked to inflammation, is found in the white matter of multiple sclerosis (MS) patients. Its expression increases in active MS lesions, suggesting a role in this central nervous system disease.

Area of Science:

  • Neuroscience
  • Immunology
  • Biochemistry

Background:

  • ADAM-17 (a disintegrin and metalloproteinase) cleaves membrane-bound tumor necrosis factor (TNF) and other molecules.
  • TNF is a pro-inflammatory cytokine implicated in central nervous system (CNS) inflammatory diseases like multiple sclerosis (MS).

Purpose of the Study:

  • To investigate the cellular origin and distribution of ADAM-17 expression in MS white matter.
  • To correlate ADAM-17 levels with disease activity in MS.

Main Methods:

  • Immunohistochemistry, western blotting, and PCR were used to assess ADAM-17 expression.
  • Analysis was performed on white matter from MS patients and normal controls.

Main Results:

  • ADAM-17 expression was detected in endothelial cells, macrophages/microglia, and astrocytes in MS white matter.
  • Higher ADAM-17 immunoreactivity was observed in active MS lesions with recent myelin breakdown.

Conclusions:

  • ADAM-17 is present in various cell types within MS white matter.
  • ADAM-17 expression is associated with active demyelination in MS, warranting further investigation into its pathogenic role.

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