Production of IL-6 by human myoblasts stimulated with Abeta: relevance in the pathogenesis of IBM.
OBJECTIVE
To determine whether amyloid-beta protein (Abeta) can induce the production of proinflammatory cytokines by cultured normal muscle cells.


BACKGROUND
Sporadic inclusion body myositis (IBM) is characterized by the presence of rimmed vacuoles and fibrillary inclusions of Abeta in muscle fibers, and often inflammatory cells. Endomysial expression of proinflammatory molecules has suggested an ongoing immune process, but the site of sensitization and the mechanisms that trigger an inflammatory reaction is unknown.


METHODS
The authors used Northern blot analysis and specific immunoassays to study the expression and secretion in cell-free supernatants of tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) by purified human myoblasts and C2C12 mouse skeletal muscle cells incubated with Abeta[1-42] or Abeta[25-35] peptides.


RESULTS
Nonstimulated muscle cells produced detectable IL-6, whereas secretion of IL-1beta and TNFalpha was absent. Incubation with Abeta peptides increased IL-6 production, whereas TNFalpha and IL-1beta levels remained undetectable. Northern blot analysis of Abeta-stimulated human myoblasts revealed an increase in IL-6 mRNA expression.


CONCLUSIONS
Cultured muscle cells increase the constitutive production of IL-6 in response to local deposition of Abeta in sporadic IBM. IL-6 could be a CD8(+) proliferation and differentiation agent, an autocrine proteolysis-inducing factor of damaged myotubes, and a proliferation-stimulating agent for satellite cells to replace the destroyed myofibers in IBM.
Baron
P
P
Department of Neurological Sciences, Centro Dino Ferrari, University of Milan School of Medicine, IRCCS Ospedale Maggiore, Milan, Italy. neuromil@mailserver.unimi.it
Galimberti
D
D
Meda
L
L
Scarpini
E
E
Conti
G
G
Cogiamanian
F
F
Scarlato
G
G
D000328:Adult; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000276:immunology*; D018482:Muscle, Skeletal / Q000166:cytology; D018979:Myositis, Inclusion Body / Q000209:etiology* / Q000276:immunology; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012038:Regeneration / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016229:Amyloid beta-Peptides; D007375:Interleukin-1; D015850:Interleukin-6; D010446:Peptide Fragments; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42)