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Modeling time delay in the NFκB signaling pathway following low dose IL-1 stimulation

Johannes Witt1*, Sandra Barisic2, Oliver Sawodny1, Michael Ederer1, Dagmar Kulms2 and Thomas Sauter13

Author Affiliations

1 Institute for System Dynamics, University of Stuttgart, Pfaffenwaldring 9, 70569 Stuttgart, Germany

2 Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany

3 Life Sciences Research Unit, University of Luxembourg, 162a, Avenue de la Faïencerie, 1511 Luxembourg, Luxembourg

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EURASIP Journal on Bioinformatics and Systems Biology 2011, 2011:3  doi:10.1186/1687-4153-2011-3

Published: 17 June 2011


Stimulation of human epithelial cells with IL-1 (10 ng/ml) + UVB radiation results in sustained NFκB activation caused by continuous IKKβ phosphorylation. We have recently published a strictly reduced ordinary differential equation model elucidating the involved mechanisms. Here, we compare model extensions for low IL-1 doses (0.5 ng/ml), where delayed IKKβ phosphorylation is observed. The extended model including a positive regulatory element, most likely auto-ubiquitination of TRAF6, reproduces the observed experimental data most convincingly. The extension is shown to be consistent with the original model and contains very sensitive processes which may serve as potential intervention targets.

IKKbeta; TRAF6; mathematical model; IL-1; UVB