In silico Kinetic Model of iNOS Expression in Macrophages

Macrophages are a key component in the host innate response and are major contributors to the proinflammatory response against pathogens. One of the key players in the proinflammatory response is induced nitric oxide synthase (iNOS), an enzyme that provides the nitric oxide needed by phagocytic cells to create reactive nitrogen species, which are highly damaging to intracellular pathogens. To model the macrophage intracellular mechanism of iNOS gene expression, we use a systems biology approach to capture the dynamics of the iNOS gene expression system stimulated by bacterial lipopolysaccharide (LPS) and IFN-gamma. Our simulation results agree with in vitro assays of iNOS gene expression and provide a platform for further investigating the potential impact of LPS and IFN-gamma variations on macrophage effector function.