Expression and Function of Toll-Like Receptor 4 in the Endometrial Cells of the Uterus

Abstract

Prostaglandins have a central role in many endocrine functions in mammals, including regulation of the life span of the corpus luteum by prostaglandin F(2alpha) (PGF) and prostaglandin E2 (PGE), which are secreted by the uterine endometrium. However, the uterus is readily infected with bacteria such as Escherichia coli, which disrupt luteolysis. Immune cells detect E. coli by Toll-like receptor 4 (TLR4) binding its pathogenic ligand, lipopolysaccharide (LPS), although signaling requires accessory molecules such as CD14. The objective of this study was to determine the effect of E. coli or LPS on the function of bovine endometrial cells, and whether purified populations of epithelial and stromal cells express the molecules involved in LPS recognition. In addition, because the female sex hormones estradiol and progesterone modify the risk of uterine infection, their effect on the LPS response was investigated. Endometrial explants produced prostaglandins in response to LPS, with an increased ratio of PGE to PGF. Addition of LPS or E. coli to stromal and epithelial cells stimulated production of PGE and PGF and increased their cyclooxygenase 2 mRNA expression. The production of prostaglandins was abrogated by an LPS antagonist. In addition, estradiol and progesterone inhibited the production of PGE and PGF in response to LPS, indicating a role for steroid hormones in the response to bacterial infection. For the first time, Toll-like receptor 4 mRNA and CD14 mRNA and protein were detected in bovine endometrial stromal and epithelial cells by RT-PCR and flow cytometry. In conclusion, epithelial and stromal cells detect and respond to bacteria, which modulate their endocrine function.

Examination of bacterial contamination at the time of embryo transfer, and its impact on the IVF/pregnancy outcome

“…Concerning this issue, it seems particularly relevant that endometrial cells express Toll-like receptor 4, a molecule involved in Gram negative endotoxin and that E. coli binding to these cells produces prostaglandin F and E 2 , thus modulating inflammatory response and endocrine functions [21].…”

Prevalence of subclinical endometritis in repeat breeding cows and mRNA expression of tumor necrosis factor α and inducible nitric oxide synthase in the endometrium of repeat breeding cows with and without subclinical endometritis

“…Because the uterine influx of PMNs is the main element of the innate immune system involved in the resolution of infection, a rising count of these cells reflects the severity of local inflammation. In general, this defence system is activated in the presence of pathogen-associated molecules such as bacterial or viral LPS, DNA and lipids recognized by TLR-receptors (Herath et al 2006, Singh et al 2008, Sheldon et al 2009). Engagement of these receptors initiates a signalling inflammatory cascade, stimulating production of many mediators (cytokines, chemokines, prostaglandins etc.…”

Effect of Escherichia coli infection of the bovine uterus from the whole animal to the cell

“…It is the role of TLR4 to detect LPS, although signalling through TLR4 also requires accessory molecules such as CD14, LBP and MD2 (Beutler, 2003 and2004). Bovine uterine endometrial and stromal cells express TLR4 and the accessory molecules required for LPS recognition (Herath et al, 2006). Following treatment with LPS, epithelial and stromal cells respond to E. coli or LPS treatment by secreting PGE or PGF, respectively, and this effect is abrogated in the presence of Polymixin B, a compound that binds to LPS, thus reducing the amount available to bind to MD2/TLR4.…”

“…Following treatment with LPS, epithelial and stromal cells respond to E. coli or LPS treatment by secreting PGE or PGF, respectively, and this effect is abrogated in the presence of Polymixin B, a compound that binds to LPS, thus reducing the amount available to bind to MD2/TLR4. Thus, it appears that besides fulfilling an endocrine role, endometrial cells have an immune role in detecting and responding to bacterial pathogens (Herath et al, 2006). Uterine tissue explants secrete more PGE than PGF in response to LPS (Herath et al, 2006).…”

“…Thus, it appears that besides fulfilling an endocrine role, endometrial cells have an immune role in detecting and responding to bacterial pathogens (Herath et al, 2006). Uterine tissue explants secrete more PGE than PGF in response to LPS (Herath et al, 2006). It is well known that secretion of PGF, in response to endometrial oxytocin receptor activation, induces luteolysis and initiates the follicular phase of the ovarian cycle (Poyser, 1995).…”