Interferon-gamma and tumor necrosis factor-alpha sensitize primarily resistant human endometrial stromal cells to Fas-mediated apoptosis

Autor: Peter Licht, Margarita Deperschmidt, Diethelm Wallwiener, Stefanie Krenzer, Sebastian Wesselborg, Herbert Fluhr, Björn Stork, Gerburg M. Stein, Marek Zygmunt
Rok vydání: 2007
Předmět:
Zdroj: Fluhr, H, Krenzer, S, Stein, G M, Stork, B, Deperschmidt, M, Wallwiener, D, Wesselborg, S, Zygmunt, M & Licht, P 2007, ' Interferon-gamma and tumor necrosis factor-alpha sensitize primarily resistant human endometrial stromal cells to Fas-mediated apoptosis ', Journal of Cell Science, vol. 120, no. Pt 23, pp. 4126-33 . https://doi.org/10.1242/jcs.009761
ISSN: 0021-9533
Popis: Udgivelsesdato: 2007-Dec-1 The subtle interaction between the implanting embryo and the maternal endometrium plays a pivotal role during the process of implantation. Human endometrial stromal cells (ESCs) express Fas and the implanting trophoblast cells secrete Fas ligand (FASLG, FasL), suggesting a possible role for Fas-mediated signaling during early implantation. Here we show that ESCs are primarily resistant to Fas-mediated apoptosis independently of their state of hormonal differentiation. Pre-treatment of ESCs with interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha sensitizes them to become apoptotic upon stimulation of Fas by an agonistic anti-Fas antibody. Incubation of ESCs with the early embryonic signal human chorionic gonadotropin (hCG, CGB) does not influence their reaction to Fas stimulation. The sensitizing effect of IFN-gamma and TNF-alpha was accompanied by a significant upregulation of Fas and FLICE-inhibitory protein (FLIP, CFLAR) expression in ESCs. Additionally, we observed an activation of caspase 3, caspase 8 and caspase 9 upon apoptotic Fas triggering. In summary, we demonstrate that IFN-gamma and TNF-alpha sensitize primarily apoptosis-resistant ESCs to Fas-mediated cell death. This might be due to an upregulation of Fas expression, and apoptosis seems to be mediated by active caspase 3, caspase 8 and caspase 9. The observed pro-apoptotic effect of IFN-gamma and TNF-alpha on ESCs could play an important role in the modulation of early implantation.
Databáze: OpenAIRE