Summary
2011 International Symposium on Nonlinear Theory and Its Applications
2011
Session Number:A1L-E
Session:
Number:A1L-E1
Emergence of macroscopic simplicity from the Tumor Necrosis Factor-alpha signaling dynamics
Kentaro Hayashi, Vincent Piras, Masaru Tomita, Masa Tsuchiya, Kumar Selvarajoo,
pp.68-71
Publication Date:2011/9/4
Online ISSN:2188-5079
Summary:
The Tumor Necrosis Factor-α (TNF-α), a cytokine produced during the innate immune response to invading pathogens, is involved in numerous fundamental cellular processes. Here, to understand the temporal activation profiles of TNF-α regulated signaling network, we developed a dynamic computational model based on perturbation-response approach and the law of information (signaling flux) conservation. Our simulations show that the temporal average population response of the TNF-α stimulated transcription factors NF-kB and AP-1, and 3 groups of 180 downstream gene expressions follow first-order equations. Using the model, in contrast to a well-known previous study, our model suggests that the continuous activation of the third group of genes is not mainly due to the poor rate of mRNA decay process, rather, the law of signaling flux conservation stipulates the presence of secondary signaling, such as feedback mechanism or autocrine signaling, is crucial. Although the living system is perceived as sophisticated and complex, notably, our work reveals the presence of simple governing principles in cell population dynamics.