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.
Yang
C C
CC
USC Neuromuscular Center, Department of Neurology, University of Southern California School of Medicine, Good Samaritan Hospital, Los Angeles 90017-1912, USA.
Askanas
V
V
Engel
W K
WK
Alvarez
R B
RB
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