Investigation of IL-6 and IL-10 signalling via mathematical modelling.
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.
Texas A&M University, Artie McFerrin Department of Chemical Engineering, College Station, USA.
C
C
Moya
Z
Z
Huang
P
P
Cheng
A
A
Jayaraman
J
J
Hahn
D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D016753:Interleukin-10; D015850:Interleukin-6; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators
D016207:Cytokines; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D016753:Interleukin-10