title: Modeling time delay in the NFκB signaling pathway following low dose IL-1 stimulation.
abstract: 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.
authors.affiliation: Institute for System Dynamics, University of Stuttgart, Pfaffenwaldring 9, 70569 Stuttgart, Germany. witt@isys.uni-stuttgart.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Witt
authors.forename: Sandra
authors.initials: S
authors.lastname: Barisic
authors.forename: Oliver
authors.initials: O
authors.lastname: Sawodny
authors.forename: Michael
authors.initials: M
authors.lastname: Ederer
authors.forename: Dagmar
authors.initials: D
authors.lastname: Kulms
authors.forename: Thomas
authors.initials: T
authors.lastname: Sauter