Fig. 5 | npj Systems Biology and Applications

Fig. 5

From: Model-based identification of TNFα-induced IKKβ-mediated and IκBα-mediated regulation of NFκB signal transduction as a tool to quantify the impact of drug-induced liver injury compounds

Fig. 5

Model prediction of DCF-induced changes in the NFκB pathway. a Model-predicted time course of nuclear IκBα and of NFκB in response to TNFα (black line) and upon TNFα and DCF co-treatment (red line). b Model simulation of the time course of the influx to the state of nuclear NFκB (brown) and efflux due to complex formation (yellow) in response to TNFα stimulation or upon co-treatment of TNFα and DCF. c Model-predicted time course of cytoplasmic IκBα response to TNFα (black solid line) and upon TNFα and DCF co-treatment (red solid line). Depending on the cytoplasmic IκBα concentration, nuclear NFκB influx is lower or higher than IκBα influx. The threshold concentration at which IκBα influx exceeds the NFκB influx is shown as dashed black line for TNFα and as dashed red line for TNFα and DCF. Shaded areas indicate phases of higher IκBα influx leading to IκBα accumulation in the nucleus. d Model-predicted time course of active IKK (pIKK) and of inactive IKK (ppIKK) for time points up to t = 50 min. The dynamics of pIKK and ppIKK in the presence of TNFα alone (black) and the presence of TNFα and DCF (red) are displayed. The higher pIKK level for DCF treatment at late time points is reflected in the crossing of IκBα thresholds at t = 60 min

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