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Non-apoptotic Fas-induced regulation of cytokines in undifferentiated and decidualized human endometrial stromal cells depends on caspase-activity.
MedLine Citation:
PMID:  20926603     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Herbert Fluhr; Henriette Wenig; Julia Spratte; Stephanie Heidrich; Jens Ehrhardt; Marek Zygmunt
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Publication Detail:
Type:  Journal Article     Date:  2010-10-06
Journal Detail:
Title:  Molecular human reproduction     Volume:  17     ISSN:  1460-2407     ISO Abbreviation:  Mol. Hum. Reprod.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9513710     Medline TA:  Mol Hum Reprod     Country:  England    
Other Details:
Languages:  eng     Pagination:  127-34     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynecology, University of Greifswald, Sauerbruchstr., 17475 Greifswald, Germany.
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