Investigation of IL-6 and IL-10 signalling via mathematical modelling

C. Moya; Z. Huang; P. Cheng; A. Jayaraman; J. Hahn

Investigation of IL-6 and IL-10 signalling via mathematical modelling

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Investigation of IL-6 and IL-10 signalling via mathematical modelling

Author(s): C. Moya ; Z. Huang ; P. Cheng ; A. Jayaraman ; J. Hahn
DOI: 10.1049/iet-syb.2009.0060

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Author(s): C. Moya ¹ ; Z. Huang ¹ ; P. Cheng ¹ ; A. Jayaraman ¹ ; J. Hahn ¹
- Affiliations: 1: Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, USA
Source: Volume 5, Issue 1, January 2011, p. 15 – 26
DOI: 10.1049/iet-syb.2009.0060 , Print ISSN 1751-8849, Online ISSN 1751-8857

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

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Investigation of IL-6 and IL-10 signalling via mathematical modelling

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