Interleukin-15 stimulates C2 skeletal myoblast differentiation.
Interleukin-15 (IL-15) is a cytokine which is highly expressed in skeletal muscle, and which stimulates muscle protein accretion in cultured skeletal muscle fibers. Using parental C2 skeletal myoblasts, no significant effects of IL-15 on skeletal muscle differentiation were observed. To test the hypothesis that IL-15 may stimulate skeletal muscle differentiation if the strong differentiation-inducing effects of autocrine insulin-like growth factor (IGF) production were inhibited, a C2 myoblast subline (C2-pBP4) was stably transfected with an expression vector for rat IGF binding protein-4 (IGFBP-4). Differentiation responses 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 myoblasts doubled the number of differentiated muscle cells which arose. These findings indicate that IL-15 can stimulate myogenic differentiation in conditions in which the strongly differentiative effects of the IGFs are inhibited. The differentiative activity of IL-15 may be of physiological significance in conditions in which IGF concentrations are low or in which the IGFs are sequestered by binding proteins.
Quinn
L S
LS
Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Tacoma, Washington 98493, USA.
Haugk
K L
KL
Damon
S E
SE
D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism; D019409:Interleukin-15 / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects*; D051381:Rats
D018974:Insulin-Like Growth Factor Binding Protein 4; D019409:Interleukin-15