NF-kappa B-induced loss of MyoD messenger RNA: Possible role in muscle decay and cachexia

MyoD regulates skeletal muscle differentiation (SMD) and is essential for r epair of damaged tissue. The transcription factor nuclear factor kappa B (N F-kappa B) is activated by the cytokine tumor necrosis factor (TNF), a medi ator of skeletal muscle wasting in cachexia, Here, the role of NF-kappa B i n cytokine-induced muscle degeneration was explored. In differentiating C2C 12 myocytes, TNF-induced activation of NF-kappa B inhibited SMD by suppress ing MyoD mRNA at the post-transcriptional level. In contrast, in differenti ated myotubes, TNF plus interferon-gamma (IFN-gamma) signaling was required for NF-kappa B-dependent down-regulation of MyoD and dysfunction of skelet al myofibers. MyoD mRNA was also down-regulated by TNF and IFN-gamma expres sion in mouse muscle in vivo. These data elucidate a possible mechanism tha t may underlie the skeletal muscle decay in cachexia.