Universiteit Leiden

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Dissertation

Dynamics of TNFalpha signaling and drug-related toxicity

In previous studies at our laboratory it was demonstrated that drug exposure of HepG2 cells can lead to an altered TNFα-induced NF-κB oscillatory phenotype, concurrent with a synergistically increased sensitivity for TNFα-induced apoptosis.

Author
Huppelschoten, S.
Date
06 December 2017
Links
Thesis in Leiden Repository

In previous studies at our laboratory it was demonstrated that drug exposure of HepG2 cells can lead to an altered TNFα-induced NF-κB oscillatory phenotype, concurrent with a synergistically increased sensitivity for TNFα-induced apoptosis. We have also shown that synergistic drug/ TNFα-induced cell death is dependent on concurrent cellular stress responses. To monitor these stress responses, we have developed a fluorescent protein stress response reporter platform, feasible for high throughput approaches. In this thesis, we focus on an in vitro HepG2 cell model, in which the addition of TNFα reflects inflammatory stress. We studied inflammatory signaling, both for use in improved in vitro testing approaches and to gain mechanistic understanding of TNFα-induced signaling in hepatocytes.

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