Human decidual cell Toll-like receptor signaling in response to endotoxin: The effect of progestins

Abstract

Objective-To determine if progesterone (P), 17-α-hydroxyprogesterone (17OHP) and 17-α hydroxyprogesterone caproate (17OHPC) modulate the Toll-like receptor (TLR) pathway in the response of decidua to lipopolysaccharide.Study Design-Cultured human decidual cells were incubated under control conditions, lipopolysaccharide alone, or pretreatment with each of the three progestins. Relative expression of 113 genes in the TLR pathway was determined using microarray.Results-We failed to demonstrate a suppression of TLR gene pathway expression in human decidual cells in response to lipopolysaccharide when pretreated with progestins. Pretreatment with each progestin prior to lipopolysaccharide resulted in a relative increase in the expression of the proapoptotic molecule, CASP8. There were no differences among the progestins.Conclusions-Our data do not support suppression of TLR pathways as a mechanism for the benefit of 17OHPC. Increased CASP8 gene expression raises the possibility that progestins "prime" the decidual cell to respond with a NFκB-mediated inflammatory response.

Oestrogen and progesterone regulation of inflammatory processes in the human endometrium

“…There are few reports examining the role of steroid hormones in the regulation of TLR expression and/or modulation of their activity in endometrium. However, TLR4 mRNA expression in endometrial stromal cells is reported to be increased by progesterone [103], which would be consistent with increased expression in the secretory phase although progestins have been reported to have no effect on the response of decidual stromal cells to LPS [111]. Oestrogen has been shown to suppress the response of the endometrial epithelial RL95-2 cell line to poly I:C, a mimic of viral infection [112].…”

Current concepts in maternal-fetal immunology: Recognition and response to microbial pathogens by decidual stromal cells

“…Krikun et al reported that LPS and other microbial ligands induced NF-κB translocation to the nucleus in DSCs, supporting a functional role for TLR 4 in these cells [17]. With regards to additional transcriptional effects, studies using primary human DSCs have illustrated that LPS increases the expression of a number of genes in the NF-κB pathway, including monocyte chemoattractant protein-1 (MCP-1) [31], IL-1β [31, 32], colony stimulating factor-2 (CSF-2) [31] and IL-8 [16, 31]. Other studies utilizing primary human DSCs observed increased gene expression of TNF-α [32, 33], IL-6 [17, 32, 33], lipid metabolism genes ( e.g.…”

Comprehensive analysis of the transcriptional response of human decidual cells to lipopolysaccharide stimulation

“…At the start of all experiments each plate contained approximately 1 × 10 6 cells. Time response experiments were performed with exposure of cells to 10 ng/mL of LPS at baseline, 2 and 24 h (Makhlouf and Simhan, 2006; Simhan et al, 2008; Linjawi et al, 2004). RNA was extracted at each time point.…”