title: Rel A/p65 is required for cytokine-induced myotube atrophy.
abstract: Muscle atrophy can be triggered by systemic illnesses that are associated with elevated proinflammatory/catabolic cytokines, which, in turn, are thought to contribute to muscle wasting. In this study, we found that the prototypical NF-κB transcription factor, Rel A (p65), is required for NF-κB activation in C2C12 and L6 myotubes due to treatment with exogenous TNF-α, IL-1α, IL-1β, TNF-related weak inducer of apoptosis, but not IL-6. All five cytokines induced atrophy in C2C12 myotubes, and inhibition of p65 reversed atrophy due to TNF-α, IL-1α, IL-1β, TNF-related weak inducer of apoptosis, but not IL-6 treatment. p65 was also required for TNF-α-induced increase in atrophy and inflammatory gene expression. TNF-α- and IL-1β-treated myotubes increased IL-6 protein expression, but use of an IL-6 blocking antibody showed that the IL-6 production did not contribute to atrophy. These data show that p65 is a required transcription factor mediating the catabolic effects of four different cytokines in cultured myotubes, but IL-6 works by a different mechanism.
authors.affiliation: Department of Health Sciences, Boston University, Massachusetts 02215, USA.
authors.forename: Takuo
authors.initials: T
authors.lastname: Yamaki
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Wu
authors.forename: Michael
authors.initials: M
authors.lastname: Gustin
authors.forename: Jamie
authors.initials: J
authors.lastname: Lim
authors.forename: Robert W
authors.initials: RW
authors.lastname: Jackman
authors.forename: Susan C
authors.initials: SC
authors.lastname: Kandarian
mesh_terms: D000818:Animals; D001284:Atrophy / Q000209:etiology / Q000473:pathology; D002460:Cell Line; D016207:Cytokines / Q000633:toxicity*; D055785:Gene Knockdown Techniques; D053582:Interleukin-1alpha / Q000502:physiology; D053583:Interleukin-1beta / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D007739:L Cells; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D032446:Myoblasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051381:Rats; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D016207:Cytokines; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha