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

TNFα-induced NFκB signaling pathway model for HepG2 cells and primary human hepatocytes (PHH). a Schematic representation of the model according to Systems Biology Graphical Notation indicating the considered components and reactions. Arrows indicate biochemical reactions. Boxes with round corners symbolize proteins, parallelograms represent RNA. Slashed circles represent degradation or production. Experimental data was acquired by either live-cell fluorescence microscopy (b) of NFκB translocation (cytoplasm and nuclei, n？=？3) and of A20 expression dynamics (n？=？1) in HepG2 cells stably expressing NFκB-GFP or A20-GFP, respectively, or quantitative immunoblotting (c–e) of cytoplasmic lysates of HepG2 cells (c, n？=？3–6, raw data in Figs. S8–S17) and PHHs (d, n？=？3 donors, raw data in Figs. S18–S21) or immunoprecipitations (e, n？=？1–3, raw data in Figs. S22–S29) treated with TNFα (10？ng/ml). Data points with 1σ confidence intervals computed from replicates are indicated by dots with error bars, lines indicate trajectories of the calibrated mode