Direct effects of tumor necrosis factor alpha (TNF-alpha) on L6 myotubes

Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine responsible for a diverse range of signaling events within cells. We studied direct effects of TNF-alpha on skeletal muscle protein content. Incubation of the L6 myotubes with 1 to 10 U/ml of TNF-alpha resulted in a significant increase of total and myofibrillar protein contents as compared with the control. However, incubation with lower (0.001-0.1 U/ ml) or higher (100-300 U/ml) doses of TNF-alpha resulted in a decrease of protein content. These findings suggest that TNF-alpha may elicit both anabolic and catabolic effects on L6 myotubes in a dose dependent manner. The anabolic effect of TNF-alpha was mediated at least in part by mitogen activated protein kinase (MAPK), especially by an extracellular-regulated kinases (ERK). This divergent effect of TNF-alpha may be crucial to elucidate the complexity of TNF-alpha action on the skeletal muscle.