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SHR Neuro Cancer Cardio Lipid Metab Microb

Fluhr, H; Wenig, H; Spratte, J; Heidrich, S; Ehrhardt, J; Zygmunt, M.
Non-apoptotic Fas-induced regulation of cytokines in undifferentiated and decidualized human endometrial stromal cells depends on caspase-activity
MOL HUM REPROD. 2011; 17(2): 127-134. Doi: 10.1093/molehr/gaq082
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Leading authors Med Uni Graz: Fluhr Herbert
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Abstract:: Fas has originally been described as a member of the death-receptor family, mediating apoptosis upon stimulation by Fas-ligand (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 17 beta-estradiol and incubated with an activating anti-Fas antibody, recombinant FasL and a caspase-inhibitor. Leukemia inhibitory factor (LIF), interleukin (IL)-II, -6, -8, monocyte chemoattractant protein (MCP)-I 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)-kappa B was detected by in-cell western and transcription factor assays. LIF and IL-II in undifferentiated and IL-8 in decidualized ESCs were up-regulated by non-apoptotic Fas-signaling. In contrast, IL-6, MCP-I and RANTES were not regulated by Fas. Caspases were activated upon Fas-stimulation and the Fas-mediated effects on LIF, IL-II and -8 were reversed by caspase-inhibition. The transcription factor NF-kappa B 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.
Find related publications in this database (Keywords): apoptosis; caspases; cytokines; endometrium; Fas