Non-apoptotic Fas-induced regulation of cytokines in undifferentiated and decidualized human endometrial stromal cells depends on caspase-activity
| Autor: | Julia Spratte, Jens Ehrhardt, Herbert Fluhr, Marek Zygmunt, Stephanie Heidrich, Henriette Wenig |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Embryology
medicine.medical_specialty Stromal cell Fas Ligand Protein medicine.medical_treatment T cell Apoptosis Enzyme-Linked Immunosorbent Assay Polymerase Chain Reaction Fas ligand Antibodies Endometrium Internal medicine Genetics medicine Humans fas Receptor Molecular Biology Transcription factor reproductive and urinary physiology Caspase Cells Cultured biology NF-kappa B Obstetrics and Gynecology Cell Biology Caspase Inhibitors Cell biology Up-Regulation Cytokine Endocrinology medicine.anatomical_structure Reproductive Medicine embryonic structures biology.protein Cytokines Female Stromal Cells Leukemia inhibitory factor Developmental Biology Signal Transduction |
| Zdroj: | Molecular human reproduction. 17(2) |
| ISSN: | 1460-2407 |
| Popis: | 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 17β-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 up-regulated 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-κB 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. |
| Databáze: | OpenAIRE |
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