Computational modeling of cytokine signaling in microglia.

ABSTRACT: Neuroinflammation due to glial activation has been linked to many CNS diseases. We developed a computational model of a microglial cytokine interaction network to study the regulatory mechanisms of microglia-mediated neuroinflammation. We established a literature-based cytokine network, including TNFα, TGFβ, and IL-10, and fitted a mathematical model to published data from LPS-treated microglia. The addition of a previously unreported TGFβ autoregulation loop to our model was required to account for experimental data. Global sensitivity analysis revealed that TGFβ- and IL-10-mediated inhibition of TNFα was critical for regulating network behavior. We assessed the sensitivity of the LPS-induced TNFα response profile to the initial TGFβ and IL-10 levels. The analysis showed two relatively sh

SUBMITTER: Anderson WD 

PROVIDER: S-EPMC5520540 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature