Proefschrift
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.
- Auteur
- Huppelschoten, S.
- Datum
- 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.