Immunolocalization and activation of transcription factor nuclear factor kappa B in dysimmune neuropathies and familial amyloidotic polyneuropathy.
BACKGROUND
Recently, immunoreactivity of transcription factor nuclear factor kappaB (NF-kappaB) was found in peripheral nerves from patients with Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), and familial amyloidotic polyneuropathy (FAP), suggesting a role in their pathogenesis.


OBJECTIVE
To investigate expression and activation of NF-kappaB in nerve biopsy specimens from patients with peripheral neuropathies of different origins.


METHODS
Nerve biopsies from 17 patients (5 with CIDP, 3 with vasculitis, 4 with Charcot-Marie-Tooth disease, and 5 with FAP) and 3 normal sural nerves were studied by immunocytochemistry and Western blot of nuclear extracts for the activated form of NF-kappaB. Nuclear factor kappaB DNA-binding activity was studied by electrophoretic mobility shift assay.


RESULTS
Immunobinding for the activated form p65 of NF-kappaB was found in 2% to 5% of endoneurial vessel walls, in the external myelin of 5% to 10% of fibers, and in a few axons in CIDP specimens. It was also found in 5% to 15% of epineurial and endoneurial vessels in vasculitis specimens and at the level of amyloid deposits in FAP nerves. Nuclear factor kappaB immunoreactivity was not correlated to type of inflammatory cells, but it often corresponded to the deposition of the terminal complement complex C5b9. Western blot analysis of nuclear extracts showed a single band corresponding to 65 kDa in all affected nerves. Nuclear factor kappaB DNA-binding activity was revealed by electrophoretic mobility shift assay in specimens from patients with CIDP, vasculitis, and FAP.


CONCLUSIONS
Our novel findings suggest a crucial role of NF-kappaB in inflammatory neuropathies and FAP.
Mazzeo
Anna
A
Department of Neuroscience, Psychiatry, and Anesthesiology, Clinica Neurologica 2, Policlinico Universitario, University of Messina, 98125 Messina, Italy. annamazzeo@yahoo.it
Aguennouz
Mohammed
M
Messina
Corrado
C
Vita
Giuseppe
G
D000328:Adult; D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000378:metabolism*; D002908:Chronic Disease; D020275:Guillain-Barre Syndrome / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000378:metabolism*; D013497:Sural Nerve / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
D016328:NF-kappa B