Receptor for advanced glycation endproduct (RAGE)-mediated nuclear factor-kappaB activation in vasculitic neuropathy.
Binding of ligands to the receptor for advanced glycation endproducts (RAGE) results in activation of the proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) and subsequent expression of NF-kappaB-regulated cytokines. In order to determine whether engagement of RAGE contributes to the pathogenesis of vasculitic neuropathy, we studied the presence of the RAGE ligand N(epsilon)-(carboxymethyl)lysine (CML), the receptor itself, NF-kappaB, and interleukin-6 (IL-6) in sural nerve biopsies of 12 patients with vasculitic neuropathies and 12 controls. In the patients, CML, RAGE, NF-kappaB, and IL-6 were localized in mononuclear cells, epineurial and endoneurial vessels and the perineurium. CML, RAGE, NF-kappaB, and IL-6 were expressed by CD4(+), CD8(+), and CD68(+) cells invading the nerves. Controls showed only weak staining. These data suggest that the RAGE pathway plays a critical proinflammatory role in vasculitic neuropathy.
Haslbeck
Karl-Matthias
KM
Department of Neurology, University of Erlangen Nürnberg, Erlangen, Germany.
Bierhaus
Angelika
A
Erwin
Schliecher
S
Kirchner
Annette
A
Nawroth
Peter
P
Schlötzer
Ursula
U
Neundörfer
Bernhard
B
Heuss
Dieter
D
D000328:Adult; D000368:Aged; D002607:Charcot-Marie-Tooth Disease / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D013497:Sural Nerve / Q000378:metabolism / Q000473:pathology; D014657:Vasculitis / Q000150:complications / Q000378:metabolism* / Q000473:pathology
D015850:Interleukin-6; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C048496:N(6)-carboxymethyllysine; D008239:Lysine