Beneficial synergistic interactions of TNF-α and IL-6 in C2 skeletal myoblasts -: Potential cross-talk with IGF system

被引:45
作者
Al-Shanti, Nasser [1 ]
Saini, Amarjit [1 ]
Faulkner, Steve H. [1 ]
Stewart, Claire E. [1 ]
机构
[1] Manchester Metropolitan Univ, Inst Biomed Res Human Movement & Hlth, Alsager ST7 2HL, Cheshire, England
关键词
TNF-alpha; IL-6; proliferation; survival; signal transducer gp130; differentiation;
D O I
10.1080/08977190802025024
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The interaction effects of tumour necrosis factor-alpha (TNF-) and interlukin-6 (IL-6) on skeletal muscle proliferation and differentiation remains controversial. We therefore investigated the potential interactive effects of TNF-alpha and IL-6 on murine C2 skeletal myoblast survival, differentiation and proliferation. A novel and unexpected positive temporal interaction between TNF-alpha and IL-6 on cell growth was identified (90%), with maximal beneficial effects obtained in myoblasts treated with TNF-alpha (10 ng/ml) for 24h prior to being dosed with IL-6 (2.5ng/ml) for a further 24h. This combined treatment significantly (p < 0.05) increased the level of total cellular protein (330%), extracellular signal-regulated kinase (ERK) phosphorylation (55%), and S-phase of cell cycle (2.5-fold), confirming cell growth. The expression of mRNAs of key regulators of muscle mass: insulin-like growth factor binding protein-5, insulin-like growth factor-II (IGF-II), IGF-I receptor (IGF-IR) and IGF-II receptor (IGF-IIR) were also significantly (p < 0.05) increased by 1600-, 1.6-, 27- and 6-fold, respectively, giving an indication of the regulatory mechanisms of this interaction. Moreover, in response to this treatment, the expression level of signal-transducing glycoprotein 130 (gp130) was induced up to 3.5-fold but not after either treatments alone. This may not only explain the beneficial effects of this treatment on skeletal myoblast numbers but also define a functional role of gp130 in skeletal muscle cells. Our data suggest that in the presence of TNF-alpha/IL-6 functions positively and potentially also cooperatively with the IGF system to achieve the maximal beneficial effect on skeletal myoblast numbers.
引用
收藏
页码:61 / 73
页数:13
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