Fig. 6 | npj Systems Biology and Applications

Fig. 6

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. 6

Application of the dynamic pathway model to additional DILI compound data. a Impact of four selected compounds, amiodarone (AMD, 35 µM), paracetamol (APAP, 10 mM), ximelagatran (XIM, 800 µM), and fialuridine (FIAU, 500 µM), on cytoplasmic IκBα, pIκBα, pIKK, and pNFĸB levels were measured by quantitative immunoblotting in HepG2 cells treated with either TNFα alone (10 ng/ml) or TNFα (10 ng/ml) and the respective compound (n = 3–4, raw data in Figs. S30–S45). Data points with 1σ confidence intervals are shown as dots and error bars in different colors for different compounds, black indicating the TNFα treatment alone. The model fit for the reduced compound-impact model is shown as solid line. Model calibration involves only experiment-specific observation parameters and the two compound-specific effect parameters α and β. b The model-predicted dynamics of nuclear NFκB for a time period of 4 h based on the short-term measurements per compound are shown as solid lines. Data points with 1σ confidence intervals for TNFα-treated cells and cells co-treated with TNFα and DCF are shown as dots with error bars

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