INTERLEUKIN-15 - A NOVEL ANABOLIC CYTOKINE FOR SKELETAL-MUSCLE

被引:215
作者
QUINN, LS
HAUGK, KL
GRABSTEIN, KH
机构
[1] UNIV WASHINGTON,DEPT MED,DIV GERONTOL & GERIATR MED,SEATTLE,WA 98195
[2] IMMUNEX RES & DEV CORP,SEATTLE,WA 98101
关键词
D O I
10.1210/en.136.8.3669
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 [H-3]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.
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页码:3669 / 3672
页数:4
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