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Fig. 4 | Cell Communication and Signaling

Fig. 4

From: Response to IL-6 trans- and IL-6 classic signalling is determined by the ratio of the IL-6 receptor α to gp130 expression: fusing experimental insights and dynamic modelling

Fig. 4

Improved parameterisation and refinement of set-based parameter estimation, based on Monte Carlo sampling. a Results for outer-bounding of model parameters. Initial parameter bounds (green bar) range from 10− 9 (lower bound, lb) to 103 (upper bound, ub). Dark grey, blue and red bars depict parameter ranges for the individual parameters after set-based analyses of the initial models. Light grey, light blue and light red bars depict parameter ranges after parameter estimation of the reduced models disregarding the SOCS3-mediated feedback. Dotted bars show final set-based estimation results for the calibrated model. Magenta plus signs depict exemplary valid Monte Carlo samples and black horizontal lines show the newly obtained parameter ranges after model refinements. b 150 out of 150,000 Monte Carlo samples that yield the lowest quadratic distance between model predictions and experimental data and reasonable represent all experimental data available. Model outputs (light and dark grey corridors) were plotted against experimental data (red and blue) presented in Figs. 1 and 4. c Model predictions for dose-dependent phosphorylation of STAT3 in response to 30 min classic (dark grey) and trans-signalling (light grey) based on the 150 Monte Carlo samples from (A). HepG2 cells were stimulated with indicated amounts of IL-6 (blue bars) or Hy-IL-6 (red bars). STAT3 phosphorylation was evaluated by intracellular flow cytometry using specific fluorescent antibodies against STAT3 (p)Y705. For independent experiments mean fluorescence of 104 cells per cytokine concentration was calculated. Data are given as mean ± STD from n = 3 experiments. The grey box depicts experimental conditions used in Fig. 1 (stimulation with 0.08 nM and 0.17 nM cytokine for 30 min)

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