Investigation of IL-6 and IL-10 signalling via mathematical modelling.
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abstract
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 CEBP is correlated with an increase of fat content and steatosis. It is known that STAT3 and CEBP 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-CEBP pathway model is extended to also include the activated transcription factor CEBP in the nucleus. Since IL-10 signals through the Jak-STAT but not the Erk-CEBP 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-CEBP was investigated for different stimulation levels of IL-6 and IL-10.
