Mathematical Simulation of Dynamics of Macrophage Gene Network Activated by Lipopolysaccharides and/or Interferon-g

Abstract

Macrophage activation is an important component of the immune response. The gene network controlling activation of macrophages comprises a large number of genes, proteins, and metabolites interacting with one another and regulating a variety of reactions. Using the GeneNet technology (Kolchanov et al., 2000), we developed a formalized description of the gene network regulating macrophage activation stimulated by lipopolysaccharides and (LPS) and interferon-γ (IFN-γ). In the concept of generalized chemical kinetic simulation approach (Likhoshvai et al.,2001), the mathematical model describing dynamics of this gene network was constructed basing on the information accumulated in GeneNet. This model allows the data on the structure—function organization of gene network, mechanisms of individual reactions, and the known values of static parameters and dynamic characteristics to be taken into account. The current version of this model comprises description of 306 elementary processes involving 36 genes, over 100 proteins and protein complexes, and other substances. The model allows specific operation patterns of the gene network in norm and during several pathologies to be investigates and concentrations of various compounds a quiescent and an activated cells to be calculated.