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This paper provides a systems level integration of the molecular events subject to reversible oxidation during IL-4 signal transduction. Code for simulation provided.

Incomplete reduction of oxygen during respiration results in the formation of highly reactive molecules known as reactive oxygen species (ROS) that react indiscriminately with cellular components and adversely affect cellular function. For a long time ROS were thought solely to be undesirable byproducts of respiration. Indeed, high levels of ROS are associated with a number of diseases. Despite these facts, antioxidants, agents that neutralize ROS, have not shown any clinical benefits when used as oral supplements. This paradox is partially explained by discoveries over the last two decades demonstrating that ROS are not always detrimental and may be essential for controlling physiological processes like cell signaling. However, the mechanisms by which ROS react with biomolecules are not well understood. In this work we combined biological experiments with novel computational methods to identify the most important mechanisms of ROS-mediated regulation in the IL-4 signaling pathway of the immune system. We developed a detailed computer model of the IL-4 pathway and its regulation by ROS dependent and independent methods. Our work enhances the understanding of principles underlying regulation of cell signaling by ROS and has potential implications in advancing therapeutic methods targeting ROS and their adverse effects.


The matlab files for reproducing the simulation results depicted in Figures 5 and S6 of the publication. These files consist of a Simbiology .sbproj project file, the .dat data files that contain measurements of phospho-STAT6, total STAT6, and SOCS levels, a script for plotting the simulation results overlaid with data.

Conditions included:
MG132 + IL4
PBS + H2O2/IL4

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