Pelosi Michele, De Rossi Manuela, Barberi Laura, Musarò Antonio
Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM, Sapienza University of Rome, Via A. Scarpa 16, 00161 Rome, Italy.
Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM, Sapienza University of Rome, Via A. Scarpa 16, 00161 Rome, Italy ; Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy.
Biomed Res Int. 2014;2014:206026. doi: 10.1155/2014/206026. Epub 2014 May 21.
IL-6 is a multifaceted pleiotropic cytokine, which is produced by a variety of cell types and targets different cells and tissues. In physiological conditions, IL-6 can be locally and transiently produced by skeletal muscle and plays an important role in muscle homeostasis. Circulating IL-6 levels are normally very low or undetectable but are dramatically increased in several pathologic conditions. In this study, we aimed to define the potential molecular mechanisms underlying the effects of IL-6 on myogenic program. We explored the molecular mechanisms through which exogenous IL-6, or the conditioned medium from the murine C-26 adenocarcinoma cells (a cellular model that secretes high levels of IL-6 and induces cancer cachexia in mice), interferes with the myogenic program. Our study revealed that IL-6 induces the activation of the Stat3 signaling and promotes the downmodulation of the p90RSK/eEF2 and mTOR/p70S6K axes, while it does not affect the activation of AKT. We thus identified potential molecular mediators of the inhibitory effects of IL-6 on myogenic program.
白细胞介素-6（IL-6）是一种具有多方面作用的多效性细胞因子，由多种细胞类型产生，并作用于不同的细胞和组织。在生理条件下，IL-6可由骨骼肌局部短暂产生，并在肌肉稳态中发挥重要作用。循环中的IL-6水平通常非常低或检测不到，但在几种病理状态下会显著升高。在本研究中，我们旨在确定IL-6对成肌程序产生影响的潜在分子机制。我们探究了外源性IL-6或小鼠C-26腺癌细胞的条件培养基（一种分泌高水平IL-6并在小鼠中诱导癌症恶病质的细胞模型）干扰成肌程序的分子机制。我们的研究表明，IL-6诱导Stat3信号通路的激活，并促进p90RSK/eEF2和mTOR/p70S6K轴的下调，而它不影响AKT的激活。因此，我们确定了IL-6对成肌程序产生抑制作用的潜在分子介质。
