Tumor necrosis factor-alpha-converting enzyme is expressed in the inflamed peripheral nervous system.

Tumor necrosis factor-alpha (TNF-alpha) is considered to play a critical role in the pathogenesis of immune-mediated inflammatory demyelinating disorders of the peripheral nervous system (PNS). Processing of membrane-bound inactive pro-TNF-alpha into the active soluble cytokine is mediated by a sheddase, the so-called TNF-alpha-converting enzyme (TACE), a member of the A Disintegrin and Metalloproteinase (ADAM) family. We explored the expression of TACE (ADAM-17) in sciatic nerves from Lewis rats with experimental autoimmune neuritis (EAN), an animal model of the Guillain-Barré syndrome (GBS), an immune-mediated polyradiculoneuropathy.

ADAM-10 and ADAM-17 in the inflamed human CNS.

Inflammatory demyelinating disorders of the CNS, such as multiple sclerosis (MS), are mediated, at least in part, by various cytokines and proteases. In the present study, we investigated the expression of A disintegrin and metalloproteinase (ADAM)-17, an important sheddase for various proteins, including tumor necrosis factor-alpha (TNF-alpha), and the p75- and p55-TNF receptors, as well as ADAM-10, a protease implicated in myelin degradation, in post mortem CNS tissue samples from patients with MS, and normal brain tissue (as control) by immunohistochemistry. ADAM-10 was found to be expressed by astrocytes in all MS and control sections studied; however, in some MS sections, perivascular macrophages were determined as an additional cellular source as well.