Fas has originally been described as a member of the death-receptor family, mediating apoptosis upon stimulation by Fasligand (FasL). However, Fas expressing human endometrial stromal cells (ESCs) are resistant to Fas-mediated apoptosis. Since the implanting embryo secretes FasL, we examined whether Fas mediates non-apoptotic effects in human ESCs in vitro. ESCs were isolated from hysterectomy specimens, decidualized using progesterone and 17b-estradiol and incubated with an activating anti-Fas antibody, recombinant FasL and a caspase-inhibitor. Leukemia inhibitory factor (LIF), interleukin (IL)-11, -6, -8, monocyte chemoattractant protein (MCP)-1 and RANTES (Regulated on Activation Normal T cell Expressed and Secreted) were measured using ELISA and real-time RT-PCR. Viability of ESCs was determined using an MTT assay. Caspase-activity was measured by luminescent assays. Activation of nuclear factor (NF)-κB was detected by in-cell western and transcription factor assays. LIF and IL-11 in undifferentiated and IL-8 in decidualized ESCs were upregulated by non-apoptotic Fas-signaling. In contrast, IL-6, MCP-1 and RANTES were not regulated by Fas. Caspases were activated upon Fas-stimulation and the Fas-mediated effects on LIF, IL-11 and -8 were reversed by caspase-inhibition. The transcription factor NF-kB was not activated in ESCs after stimulation of Fas. These results suggest a differential regulatory role of caspase-dependent Fas-signaling at the feto-maternal interface during early implantation. Remarkably, this typical death machinery mediates non-apoptotic effects in the human endometrium rather than inducing apoptosis. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
CITATION STYLE
Fluhr, H., Wenig, H., Spratte, J., Heidrich, S., Ehrhardt, J., & Zygmunt, M. (2011). Non-apoptotic Fas-induced regulation of cytokines in undifferentiated and decidualized human endometrial stromal cells depends on caspase-activity. Molecular Human Reproduction, 17(2), 127–134. https://doi.org/10.1093/molehr/gaq082
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