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

Biomedical Research Centre, Sheffield Hallam University, Howard St, Sheffield S1 1WB, UK, j.plumb{at}shu.ac.uk

S McQuaid

Neuropathology Laboratory, Department of Pathology, Royal Group of Hospitals Trust, Grosvenor Road, Belfast, Northern Ireland, UK

A K Cross

Biomedical Research Centre, Sheffield Hallam University, Howard St, Sheffield S1 1WB, UK

J Surr

Biomedical Research Centre, Sheffield Hallam University, Howard St, Sheffield S1 1WB, UK

G Haddock

Biomedical Research Centre, Sheffield Hallam University, Howard St, Sheffield S1 1WB, UK

R AD Bunning

Biomedical Research Centre, Sheffield Hallam University, Howard St, Sheffield S1 1WB, UK

M N Woodroofe

Biomedical Research Centre, Sheffield Hallam University, Howard St, Sheffield S1 1WB, UK

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.

Key Words: ADAM-17 • adhesion molecules • astrocytes • endothelium • multiple sclerosis • TACE • tumour necrosis factor

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