TNF-α is a mitogen in skeletal muscle

Emerging evidence suggests that tumor necrosis factor (TNF)-alpha plays a role in muscle repair. To determine whether TNF-alpha modulates satellite cell proliferation, the current study evaluated TNF-alpha effects on DNA synthesis in primary myoblasts and on satellite cell activation in adult mouse muscle. Exposure to recombinant TNF-alpha increased total DNA content in rat primary myoblasts dose-dependently over a 24-h period and increased the number of primary myoblasts incorporating 5-bromo-2'-deoxyuridine (BrdU) during a 30-min pulse labeling. Systemic injection of TNF-alpha stimulated BrdU incorporation by satellite cells in muscles of adult mice, whereas no BrdU was incorporated by satellite cells in control mice. TNF-alpha stimulated serum response factor (SRF) binding to the serum response element (SRE) present in the c-fos gene promoter and stimulated reporter gene expression controlled by the same element. Our data suggest that TNF-alpha activates satellite cells to enter the cell cycle and accelerates G(1)-to-S phase transition, and these actions may involve activation of early response genes via SRF.