FIGURE 1.

Inflammation and myogenesis. While multiple cytokines are involved in coordinating the myogenic response to injury, major regulators include IL-6, TNFα, and TWEAK. High concentrations of these cytokines signaling via STAT3 and the classical NF-κB pathway (p50/p65 heterodimer) stimulate myoblast proliferation but inhibit subsequent differentiation through the degradation and destabilization of the myogenic regulatory factors MyoD and myogenin. Low concentrations of IL-6, TNFα, and TWEAK signaling through p38MAPK and the alternative NF-κB pathway (p52/RelB heterodimer) are necessary to facilitate later stages of myogenesis by stimulating myoblast differentiation and fusion. IL-6, interleukin-6; NF-κB, nuclear factor-κB; p38 MAPK, p38 mitogen-activated protein kinase; STAT3, signal transducer and activator of transcription 3; TNFα, tumor necrosis factor-α; TWEAK, TNF-like weak inducer of apoptosis.