Interleukin-15 stimulates C2 skeletal myoblast differentiation

Area of Science:

• Muscle physiology
• Cellular biology
• Endocrinology

Background:

• Interleukin-15 (IL-15) is a cytokine abundant in skeletal muscle, known to promote muscle protein synthesis.
• Previous studies showed IL-15 had no significant effect on skeletal muscle differentiation in C2 myoblasts.
• Autocrine insulin-like growth factors (IGFs) possess potent differentiation-inducing effects in skeletal muscle cells.

Purpose of the Study:

• To investigate if IL-15 can stimulate skeletal muscle differentiation when the influence of autocrine IGFs is suppressed.
• To explore the role of IL-15 in myogenic differentiation under conditions of altered IGF signaling.

Main Methods:

• Created a C2 myoblast subline (C2-pBP4) stably transfected with IGF binding protein-4 (IGFBP-4) to reduce IGF effects.
• Compared differentiation responses in C2-pBP4 cells to control C2-pLXSN cells.
• Assessed the effect of adding IL-15 to C2-pBP4 myoblasts on differentiation.

Main Results:

• Differentiation responses to both autocrine and exogenous IGFs were reduced 3- to 4-fold in C2-pBP4 cells compared to controls.
• Addition of IL-15 to C2-pBP4 myoblasts resulted in a doubling of differentiated muscle cells.
• IL-15 demonstrated a capacity to stimulate myogenic differentiation when IGF signaling was attenuated.

Conclusions:

• IL-15 can stimulate skeletal muscle differentiation, particularly when the potent effects of IGFs are inhibited.
• The differentiative activity of IL-15 may be physiologically relevant in scenarios with low IGF levels or increased IGF binding proteins.