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Abstract
The interaction effects of tumour necrosis factor-alpha (TNF-α) and interlukin-6 (IL-6) on skeletal muscle proliferation and differentiation remains controversial. We therefore investigated the potential interactive effects of TNF-α and IL-6 on murine C2 skeletal myoblast survival, differentiation and proliferation. A novel and unexpected positive temporal interaction between TNF-α and IL-6 on cell growth was identified (90%), with maximal beneficial effects obtained in myoblasts treated with TNF-α (10 ng/ml) for 24 h prior to being dosed with IL-6 (2.5 ng/ml) for a further 24 h. 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-α/IL-6 functions positively and potentially also cooperatively with the IGF system to achieve the maximal beneficial effect on skeletal myoblast numbers.
| Abbreviations | ||
| DM | = | differentiation medium |
| GM | = | growth medium |
| IGFBP-5 | = | insulin-like growth factor binding protein-5 |
| IGF-II | = | insulin-like growth factor-II |
| IGF-IIR | = | insulin-like growth factor-II receptor |
| IGF-IR | = | insulin-like growth factor-I receptor |
| IL-6 | = | interleukin-6 |
| JAKs | = | Janus kinases |
| MAPK | = | mitogen-activated protein kinase |
| STAT | = | signal transducer and activator of transcription |
| TGF-β | = | transforming growth factor beta |
| TNF-α | = | tumour necrosis factor-alpha |
| Abbreviations | ||
| DM | = | differentiation medium |
| GM | = | growth medium |
| IGFBP-5 | = | insulin-like growth factor binding protein-5 |
| IGF-II | = | insulin-like growth factor-II |
| IGF-IIR | = | insulin-like growth factor-II receptor |
| IGF-IR | = | insulin-like growth factor-I receptor |
| IL-6 | = | interleukin-6 |
| JAKs | = | Janus kinases |
| MAPK | = | mitogen-activated protein kinase |
| STAT | = | signal transducer and activator of transcription |
| TGF-β | = | transforming growth factor beta |
| TNF-α | = | tumour necrosis factor-alpha |
