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

Stimulation of human epithelial cells with IL-1 (10 ng/ml) + UVB radiation results in sustained NFkappaB activation caused by continuous IKKbeta 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 IKKbeta 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.