Investigations into the analysis and modeling of the TNF alpha-mediated NF-kappa B-signaling pathway

In this study, we propose a system-theoretic approach to the analysis and quantitative modeling of the TNFalpha-mediated NF-kappaB-signaling pathway. Tumor necrosis factor alpha (TNFalpha) is a potent proinflammatory cytokine that plays an important role in immunity and inflammation, in the control of cell proliferation, differentiation, and apoptosis. To date, there have been numerous approaches to model cellular dynamics. The most prominent uses ordinary differential equations (ODEs) to describe biochemical reactions. This approach can provide us with mathematically well-founded and tractable interpretations regarding pathways, especially those best described by enzyme reactions. This work first introduces a graphical method to intuitively represent the TNFalpha-mediated NF-kappaB-signaling pathway and then utilizes ODEs to quantitatively model the pathway. The simulation study shows qualitative validation of the proposed model compared with experimental results for this pathway. The proposed system-theoretic approach is expected to be further applicable to predict the signaling behavior of NF-kappaB in a quantitative manner for any variation of the ligand, TNFalpha.