Interleukin-15: a novel anabolic cytokine for skeletal muscle.
Interleukin-15 (IL-15) is a recently discovered growth factor which is highly expressed in skeletal muscle. In order to determine a functional role for IL-15 in skeletal myogenesis, the effects of IL-15 on myoblast proliferation and muscle-specific myosin heavy chain (MHC) expression were analyzed using the mouse C2 skeletal myogenic cell line and primary fetal bovine skeletal myogenic cultures. IL-15 had no effect on [3H]thymidine incorporation, nor on the rate of myoblast differentiation, assessed by anti-MHC immunocytochemical staining, in either type of culture. However, Western blot analyses revealed that IL-15 used at concentrations of 10 or 100 ng/ml increased MHC accumulation five-fold in C2 myoblast cultures and 2.5-fold in primary bovine myogenic cultures. Moreover, C2 myotubes formed in the presence of IL-15 appeared larger than controls. These findings indicate IL-15 can stimulate differentiated myocytes and muscle fibers to accumulate increased amounts of contractile proteins. Well-fused primary bovine myogenic cultures treated with the mitotic inhibitor aphidicolin, then administered IL-15 and/or the anabolic growth factor insulin-like growth factor-I (IGF-I), were analyzed for MHC accumulation using Western blots. IL-15 used at 10 ng/ml doubled MHC accumulation and was as effective as IGF-I used at 10 or 100 ng/ml. IL-15 and IGF-I used together increased MHC accumulation close to five-fold, indicating these two factors can act additively on muscle fibers. These findings indicate IL-15 affects parameters associated with skeletal muscle fiber hypertrophy, and suggest that IL-15 may be a novel anabolic agent to increase skeletal muscle mass.
Quinn
L S
LS
Geriatric Research, Education, and Clinical Center, American Lake VA Medical Center, Tacoma, WA 98493, USA.
Haugk
K L
KL
Grabstein
K H
KH
D000818:Animals; D002417:Cattle; D002454:Cell Differentiation; D002460:Cell Line; D016207:Cytokines / Q000502:physiology*; D000882:Haplorhini; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D019409:Interleukin-15; D007378:Interleukins / Q000502:physiology*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D009218:Myosins / Q000378:metabolism; D011994:Recombinant Proteins
D016207:Cytokines; D019409:Interleukin-15; D007378:Interleukins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D009218:Myosins