Evidence for the Presence of Toll-Like Receptor 4 System in the Human Endometrium

Hirata, Tetsuya; Osuga, Yutaka; Hirota, Yasushi; Koga, Kaori; Yokosuka, Osamu; Harada, Miyuki; Morimoto, Chieko; Yano, Tetsu; Nishii, Osamu; Tsutsumi, Osamu; Taketani, Yuji

doi:10.1210/jc.2004-0241

Cited by 93 publications

(116 citation statements)

References 35 publications

(25 reference statements)

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“…Endometrial, cervical and Fallopian tube epithelial cells have both been shown to respond to the TLR3 ligand, poly I:C, with increased cytokine output (Lesmeister et al 2005, Andersen et al 2006, Ghosh et al 2008, Nasu et al 2007. Fallopian tube fibroblasts and endometrial epithelial and stromal cells have been shown to increase inflammatory mediator output in response to LPS (lipopolysaccharide), a TLR4 ligand (Hirata et al 2005, Itoh et al 2006. These in vitro data suggest that TLRs on reproductive tract cells will be capable of responding to pathogen products in vivo.…”

Section: Toll-like Receptors (Tlrs)mentioning

confidence: 99%

Innate immunity and disorders of the female reproductive tract

Horne¹,

Stock²,

King³

2008

Reproduction

136

129

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Sexually transmitted infections, and their associated sequelae, such as tubal infertility, ectopic pregnancy and preterm labour, are a major worldwide health problem. Chlamydia trachomatis infection is thought to be the leading global cause of tubal infertility and tubal ectopic pregnancy. Preterm birth occurs in around 10% of all deliveries, and nearly 30% of preterm deliveries are associated with intrauterine infection. The mucosal innate immune system of the female reproductive tract has evolved to eliminate such sexually transmitted pathogens whilst maintaining its ability to accommodate specialized physiological functions that include menstruation, fertilization, implantation, pregnancy and parturition. The aim of this review was to describe the role and distribution of key mediators of the innate immune system, the natural antimicrobial peptides (secretory leukocyte protease inhibitor, elafin and the defensins) and the pattern recognition toll-like receptors in the normal female reproductive tract and in the context of these pathological processes.

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Section: Toll-like Receptors (Tlrs)mentioning

confidence: 99%

Innate immunity and disorders of the female reproductive tract

Horne¹,

Stock²,

King³

2008

Reproduction

136

129

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“…Isolation and culture of human EEC and ESC was as described previously (21)(22)(23)(24). Endometrial tissues were minced and incubated in DMEM/F12 containing 0.25% type I collagenase and 15 U/ml DNase I for 60 min at 37°C.…”

Section: Isolation Purification and Culture Of Endometrial Epithelimentioning

confidence: 99%

“…Flow cytometric analysis was performed as we have reported previously (22). Adherent cells (EEC, ESC, and trophoblast cells) were detached by using 0.25% trypsin/EDTA.…”

Section: Flow Cytometric Analysismentioning

confidence: 99%

The Expression and Possible Roles of Chemokine CXCL11 and Its Receptor CXCR3 in the Human Endometrium

Hirota

Osuga

Koga

et al. 2006

The Journal of Immunology

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IFN-γ secreted by a human embryo and trophoblast cells during implantation is suggested to play an important role in implantation and pregnancy. In the present study, we explored expression and possible functions of CXCL11, a CXC chemokine strongly induced by IFN-γ, and its receptor CXCR3 in the human endometrium. Secreted CXCL11 protein was not detected in cultured endometrial stromal cells (ESC) but was detected in cultured endometrial epithelial cells (EEC). IFN-γ stimulated the protein levels of CXCL11 in a dose-dependent manner in EEC and ESC. CXCL11 secreted from EEC with 100 ng/ml IFN-γ was 220-fold of the control, and 100-fold as compared with that secreted from ESC with the same dose of IFN-γ. CXCR3 was expressed in EEC, ESC, and trophoblast cells. Addition of IFN-γ to EEC increased the chemotactic activity of its culture medium to trophoblast cells and T cells, and the effect was suppressed by immunoneutralization with Abs of three CXCR3 ligands, including anti-CXCL11 Ab. CXCL11 significantly increased BrdU incorporation of ESC, which was inhibited by a p42/44 MAPK pathway inhibitor PD98059. In contrast, CXCL11 significantly decreased BrdU incorporation and increased the release of lactate dehydrogenase and the positive staining of annexin V in EEC. These findings suggest that IFN-γ promotes implantation by stimulating EEC to produce CXCL11, which induces migration of trophoblast cells and T cells, proliferation of ESC, and apoptosis of EEC.

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“…The endometrium provides a barrier against infection and an opportunity to detect bacteria by innate immune receptors recognising PAMPs (Beutler, 2004). In the human endometrium, nine TLRs are expressed at the mRNA level including TLR4 (Pioli et al, 2004;Young et al, 2004;Hirata et al, 2005;Schaefer et al, 2005). 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).…”

Section: Cellular Mechanismsmentioning

confidence: 99%

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

Williams

Herath

England

et al. 2008

Animal

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Following parturition, contamination of the uterine lumen by bacteria is ubiquitous, and uterine health is impaired in cattle because infection persists in 10% to 15% of animals as endometritis. Endometritis causes infertility for the duration of infection, and subfertility persists even after apparent successful resolution of the disease. Escherichia coli is the pathogenic bacterium most frequently isolated from the post partum uterus, and is associated with increased concentrations of peripheral plasma acute phase proteins and fetid vaginal mucus. The presence of E. coli is also associated with slower growth of the first post partum dominant follicle and perturbed oestradiol secretion. Furthermore, in animals that ovulate the first dominant follicle, the corpus luteum is smaller and secretes less progesterone. The endotoxin lipopolysaccharide (LPS), which is released from E.coli, can pass from the uterine lumen to the peripheral circulation and LPS concentrations are increased in cows with uterine infection. Infusion of E. coli LPS into the uterine lumen suppresses the pre-ovulatory luteinising hormone surge and disrupts ovulation in heifers. In vitro, endometrial explants produce prostaglandins in response to LPS. Addition of LPS or E. coli to stromal or epithelial cells increases cyclooxygenase-2 mRNA expression, and stimulates the production of prostaglandin E 2 and prostaglandin F 2a . Furthermore, uterine and ovarian cells express mRNA of the molecules required for recognition of LPS, Toll-like receptor-4 and CD14. In summary, E. coli is a common cause of infertility involving the perturbation of the hypothalamus, pituitary and ovary in dairy cows.

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Evidence for the Presence of Toll-Like Receptor 4 System in the Human Endometrium

Cited by 93 publications

References 35 publications

Innate immunity and disorders of the female reproductive tract

Innate immunity and disorders of the female reproductive tract

The Expression and Possible Roles of Chemokine CXCL11 and Its Receptor CXCR3 in the Human Endometrium

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

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