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Letter

Investigations Into the Analysis and Modeling of the TNF-Mediated NF-B-Signaling Pathway

¹ School of Electrical Engineering, University of Ulsan, Ulsan 680-749, Korea ² Immunomodulation Research Center, University of Ulsan, Ulsan 680-749, Korea ³ Department of Computer Science, University of Rostock, 18051 Rostock, Germany

In this study, we propose a system-theoretic approach to the analysis and quantitative modeling of the TNF-mediated NF-B-signaling pathway. Tumor necrosis factor (TNF) 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 TNF-mediated NF-B-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-B in a quantitative manner for any variation of the ligand, TNF.

Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.1195703. Article published online before print in October 2003.

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