Activation of nuclear factor-kappaB in inflammatory myopathies and Duchenne muscular dystrophy.
OBJECTIVE
To investigate the immunolocalization and activation of nuclear factor-kappaB (NF-kappaB) in polymyositis, dermatomyositis, and Duchenne muscular dystrophy (DMD).


BACKGROUND
NF-kappaB is a major transcription factor modulating the cellular immune, inflammatory, and proliferative responses. In skeletal muscle it was demonstrated to play a role in the expression of inducible genes in response to oxidative stress and ischemia/reperfusion injury, and also in myonuclear apoptosis and muscle catabolism. Some data suggest that NF-kappaB may play a role in the pathogenesis of inclusion body myositis.


METHODS
Muscle samples from five patients each with polymyositis, dermatomyositis, and DMD and 10 normal controls were studied by immunocytochemistry and Western blot of nuclear extracts for the activated form of NF-kappaB. NF-kappaB DNA binding activity was studied by electrophoretic mobility shift assay (EMSA).


RESULTS
Immunoreactivity for NF-kappaB was found in the cytoplasm of all regenerating fibers and in 20 to 40% of necrotic fibers. Western blot analysis of nuclear extracts showed a single band corresponding to 65 kd in all patients. EMSA analysis confirmed activation of NF-kappaB pathway in inflammatory myopathies and, to a lesser extent, also in DMD.


CONCLUSIONS
These data indicate that nuclear factor-kappaB pathway is activated in polymyositis, dermatomyositis, and Duchenne muscular dystrophy. It may play a role in modulating the immune response and in regulating myogenesis and muscle repair.
Monici
M C
MC
Department of Neurosciences, Psychiatry, and Anaesthesiology, University of Messina, Italy.
Aguennouz
M
M
Mazzeo
A
A
Messina
C
C
Vita
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002648:Child; D003593:Cytoplasm / Q000737:chemistry; D003882:Dermatomyositis / Q000378:metabolism* / Q000473:pathology; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D008264:Macrophages / Q000737:chemistry / Q000648:ultrastructure; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000473:pathology / Q000502:physiology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D009336:Necrosis; D017285:Polymyositis / Q000378:metabolism* / Q000473:pathology; D012038:Regeneration; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000648:ultrastructure
D016328:NF-kappa B