Immunolocalization of transcription factor NF-kappaB in inclusion-body myositis muscle and at normal human neuromuscular junctions.
To investigate whether nuclear factor kappaB (NF-kappaB) is involved in the pathogenesis of inclusion-body myositis (IBM), we immunostained muscle biopsies of eight patients with IBM with specific antibodies against its p50 and p65 subunits. Approximately 70% of IBM vacuolated muscle fibers had strong focal accumulations of both NF-kappaB p50 and p65, which by immunoelectronmicroscopy, localized mainly to clusters of paired-helical filaments (PHFs). Virtually all necrotic fibers, in various muscle biopsies, had diffusely strong p50 immunoreactivity, whereas p65 immunoreactivity was present only in a small subset of necrotic fibers. At all neuromuscular junctions, postsynaptically there was strong p65 but no p50 immunoreactivity. Our data suggest that NF-kappaB plays a role in IBM pathogenesis. Different distributions of NF-kappaB subunits in necrotic fibers and at normal neuromuscular junctions (NMJs) suggests different roles of each subunit in human muscle pathology and physiology.
USC Neuromuscular Center, Department of Neurology, University of Southern California School of Medicine, Good Samaritan Hospital, Los Angeles 90017-1912, USA.
C C
CC
Yang
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V
Askanas
W K
WK
Engel
R B
RB
Alvarez
D006801:Humans; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D009132:Muscles / Q000378:metabolism* / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D009336:Necrosis; D009469:Neuromuscular Junction / Q000378:metabolism* / Q000648:ultrastructure; D012016:Reference Values; D014018:Tissue Distribution
D016328:NF-kappa B