title: A minimal spatio-temporal model of the NF-κB signalling pathway exhibits a range of behaviours.
abstract: In animal cells, the transcription factor NF-κB regulates many stressful, inflammatory, and innate immune responses. Experiments have revealed that, in response to cell stimulation, NF-κB can exhibit oscillatory dynamics where the nature of these dynamics can influence the pattern of NF-κB-dependent gene expression. Oscillations in NF-κB are believed to depend on a negative feedback loop linking NF-κB and one of its downstream products, namely IκBα. This negative feedback loop is enhanced by cell stimulation. However, it also exists in the absence of cell stimulation. Here we propose a minimal spatio-temporal model of the NF-κB signalling pathway, composed of partial differential equations. Through numerical simulations, we find various combinations of behaviours before and during cell stimulation: equilibrium dynamics (rapid convergence to a solution that is everywhere constant) before cell stimulation, followed by oscillatory dynamics during cell stimulation; oscillatory dynamics before and during cell stimulation; oscillatory dynamics before cell stimulation, followed by equilibrium dynamics during cell stimulation; and equilibrium dynamics before and during cell stimulation. In each case, when cell stimulation ceases, the model quickly returns to its pre-stimulation behaviour. All of these different combinations of behaviours occur for similar sets of parameter values. Therefore, our results may help to explain why, in experiments on the NF-κB pathway involving populations of cells, only a certain fraction of the cells exhibit oscillatory dynamics.
authors.affiliation: Division of Mathematics, University of Dundee, Dundee, DD1 4HN, UK, aterry.maths@outlook.com.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Terry
mesh_terms: D000818:Animals; D002477:Cells / Q000378:metabolism; D025461:Feedback, Physiological; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D055641:Mathematical Concepts; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha