INTERLEUKIN-15 STIMULATES C2 SKELETAL MYOBLAST DIFFERENTIATION

Interleukin-15 (IL-15) is a cytokine which is highly expressed in skel etal muscle, and which stimulates muscle protein accretion in cultured skeletal muscle fibers. Using parental C2 skeletal myoblasts, no sign ificant effects of IL-15 on skeletal muscle differentiation were obser ved. To test the hypothesis that IL-15 may stimulate skeletal muscle d ifferentiation if the strong differentiation-inducing effects of autoc rine insulin-like growth factor (IGF) production were inhibited, a C2 myoblast subline (C2-pBP4) was stably transfected with an expression v ector for rat IGF binding protein-4 (IGFBP-4). Differentiation respons es to autocrine and exogenous IGFs in C2-BP4 myoblasts were reduced 3- to 4-fold in C2-BP4 cultures compared to C2-pLXSN cultures, a subline transfected with a control plasmid. Addition of IL-15 to C2-pBP4 myob lasts doubled the number of differentiated muscle cells which arose. T hese findings indicate that IL-15 can stimulate myogenic differentiati on in conditions in which the strongly differentiative effects of the IGFs are inhibited. The differentiative activity of IL-15 may be of ph ysiological significance in conditions in which IGF concentrations are low or in which the IGFs are sequestered by binding proteins. (C) 199 7 Academic Press.