Texas A&M University, Artie McFerrin Department of Chemical Engineering, College Station, USA.
IET Syst Biol. 2011 Jan;5(1):15. doi: 10.1049/iet-syb.2009.0060.
Steatosis, i.e., the accumulation of fat in hepatocytes, plays an important role in the progression of non-alcoholic fatty liver disease (NAFLD). It has been shown that STAT3 activation is involved in a decrease of lipid accumulation while C∕EBP is correlated with an increase of fat content and steatosis. It is known that STAT3 and C∕EBP are activated by IL-6 and that IL-6 signalling is also affected by IL-10, even though the exact mechanism is unclear. This paper develops a model for IL-6 and IL-10 signal transduction and then investigates the effect that stimulation with these cytokines has on the transcription factor dynamics. In an initial step, some parameters of a previously developed IL-6 signalling model are re-estimated based upon newly developed experimental data for the Jak-STAT pathway. Furthermore, the Erk-C∕EBP pathway model is extended to also include the activated transcription factor C∕EBP in the nucleus. Since IL-10 signals through the Jak-STAT but not the Erk-C∕EBP pathway, a model was developed which includes interaction between IL-6 and IL-10 signalling as both mechanisms share signal transduction through the Jak-STAT pathway. Based upon the model, the activity ratio of Jak-STAT and Erk-C∕EBP was investigated for different stimulation levels of IL-6 and IL-10.
脂肪变性，即肝细胞内脂肪堆积，在非酒精性脂肪性肝病（NAFLD）的进展中起着重要作用。已经表明 STAT3 的激活参与了脂质积累的减少，而 C∕EBP 与脂肪含量和脂肪变性的增加相关。已知 STAT3 和 C∕EBP 被 IL-6 激活，并且 IL-6 信号也受到 IL-10 的影响，尽管确切的机制尚不清楚。本文开发了一个 IL-6 和 IL-10 信号转导模型，然后研究了这些细胞因子刺激对转录因子动力学的影响。在初始步骤中，根据 Jak-STAT 途径的新开发的实验数据，重新估计了先前开发的 IL-6 信号模型的一些参数。此外，将 Erk-C∕EBP 途径模型扩展到还包括细胞核中激活的转录因子 C∕EBP。由于 IL-10 通过 Jak-STAT 而不是 Erk-C∕EBP 途径信号传递，因此开发了一个模型，其中包括 IL-6 和 IL-10 信号之间的相互作用，因为这两种机制都通过 Jak-STAT 途径共享信号转导。基于该模型，研究了不同 IL-6 和 IL-10 刺激水平下 Jak-STAT 和 Erk-C∕EBP 的活性比。
