Abstract
The Myeloid Differentiation Primary-Response Protein 88 (MyD88)-dependent and— independent pathways induce proinflammatory cytokines when toll-like receptor 4 (TLR4) is activated through lipopolysaccharide (LPS) stimulus. Recent studies have implicated a crosstalk mechanism between the two pathways. However, the exact location and nature of this interaction is poorly understood. Using my previous ordinary differential equations-based computational model of the TLR4 pathway, I investigated the roles played by the various proposed crosstalk mechanisms by comparing in silico nuclear factor κB (NF-κB) and Mitogen-Activated Protein (MAP) kinases dynamic activity profiles with experimental results under various conditions in macrophages to LPS stimulus (MyD88 deficient, TRAF-6 deficient etc.). The model that best represents the experimental findings suggests that the pathways interact at more than one location: (i) TRIF to TRAF-6, (ii) TRIF-RIP1-IKK complex and (iii) TRIF to cRel via TBK1.
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Selvarajoo, K. (2013). Decoding the Signaling Mechanism of Toll-Like Receptor 4 Pathways in Wild Type and Knockouts. In: E-Cell System. Molecular Biology Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6157-9_10
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DOI: https://doi.org/10.1007/978-1-4614-6157-9_10
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