Progesterone enhances HLA-G gene expression in JEG-3 choriocarcinoma cells and human cytotrophoblasts in vitro

Yie, Shang-mian; Li, Liang-hong; Li, Guangming; Xiao, Rong; Librach, Clifford L.

doi:10.1093/humrep/dei305

Cited by 80 publications

(68 citation statements)

References 27 publications

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“…Cytokines such as interferons (IFN-alpha, IFN-beta, IFN-gamma) , tumor necrosis factor-alpha (Yang et al, 1995), IL-10 (Moreau et al, 1999), leukemia inhibitory factor (Bamberger et al, 2000) and hormones (e.g. progesterone and glucocorticoids) Yie et al, 2006a) are capable of enhancing steady-state levels of HLA-G on trophoblast cells. Here, we provide evidence that gal-1, a lectin with a potent role in modulating immune tolerance during mammalian pregnancy, has a stimulatory effect on HLA-G gene expression.…”

Section: Discussionmentioning

confidence: 99%

Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy

Tirado‐González

Freitag

Barrientos

et al. 2012

Molecular Human Reproduction

102

112

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Galectin-1 (gal-1) is expressed at the feto-maternal interface and plays a role in regulating the maternal immune response against placental alloantigens, contributing to pregnancy maintenance. Both decidua and placenta contribute to gal-1 expression and may be important for the maternal immune regulation. The expression of gal-1 within the placenta is considered relevant to cell-adhesion and invasion of trophoblasts, but the role of gal-1 in the immune evasion machinery exhibited by trophoblast cells remains to be elucidated. In this study, we analyzed gal-1 expression in preimplantation human embryos and first-trimester decidua-placenta specimens and serum gal-1 levels to investigate the physiological role played by this lectin during pregnancy. The effect on human leukocyte antigen G (HLA-G) expression in response to stimulation or silencing of gal-1 was also determined in the human invasive, proliferative extravillous cytotrophoblast 65 (HIPEC65) cell line. Compared with normal pregnant women, circulating gal-1 levels were significantly decreased in patients who subsequently suffered a miscarriage. Human embryos undergoing preimplantation development expressed gal-1 on the trophectoderm and inner cell mass. Furthermore, our in vitro experiments showed that exogenous gal-1 positively regulated the membrane-bound HLA-G isoforms (HLA-G1 and G2) in HIPEC65 cells, whereas endogenous gal-1 also induced expression of the soluble isoforms (HLA-G5 and -G6). Our results suggest that gal-1 plays a key role in pregnancy maternal immune regulation by modulating HLA-G expression on trophoblast cells. Circulating gal-1 levels could serve as a predictive factor for pregnancy success in early human gestation.

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Section: Discussionmentioning

confidence: 99%

Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy

Tirado‐González

Freitag

Barrientos

et al. 2012

Molecular Human Reproduction

102

112

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“…A few HLA-G promoter binding factors and their target sites have been characterized such as CREB1 (28), IFN regulatory factor 1 (35), heat shock transcription factor 1 (36), or progesterone receptor (37). Microenvironmental parameters have been shown to play a key role in the modulation of HLA-G gene, including stress conditions such as heat shock (36) or hypoxia (38), cytokines such as IFN (35,39), IL-10 (40), leukemia inhibitory factor (41), GM-CSF (42), and hormones such as glucocorticoids (43) or progesterone (44). However, for most of them the mechanism of action remains unknown.…”

Section: Rreb-1 Is a Transcriptionalmentioning

confidence: 99%

RREB-1 Is a Transcriptional Repressor of HLA-G

Flajollet

Poras

Carosella

et al. 2009

The Journal of Immunology

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The nonclassical HLA-G is a molecule specifically involved in immune tolerance with highly restricted tissue distribution in healthy conditions. Yet it is overexpressed in numerous tumors and in allografts with better acceptance. Major mechanisms involved in regulation of HLA-G transcription are still poorly described. Thus, to characterize these mechanisms we have developed a specific proteomic approach to identify proteins that bind differentially to the HLA-G gene promoter by promoter pull-down assay followed by spectrometry mass analysis. Among specific binding factors, we focused on RREB-1, a ras-responsive element binding protein 1. We demonstrated that RREB-1 represses HLA-G transcriptional activity and binds three ras response elements within the HLA-G promoter. RREB-1 protein, specifically in HLA-G-negative cells, interacts with subunits of CtBP complex implicated in chromatin remodeling. This demonstration is the first of a repressor factor of HLA-G transcriptional activity taking part in HLA-G repression by epigenetic mechanisms.

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“…Signaling molecules such as progesterone, 14,15 interferon-␥, 16 and interleukin-10, 17 which are present at high levels during gestation, are capable of enhancing HLA-G expression. Interventions associated with transplantation such as hypoxic injury 18 and immunosuppressive therapy 9 might also regulate this expression.…”

mentioning

confidence: 99%

Progesterone Induces Human Leukocyte Antigen-G Expression in Vascular Endothelial and Smooth Muscle Cells

et al. 2008

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Background-Human leukocyte antigen-G (HLA-G) expression in heart transplant patients has been negatively associated with acute cellular rejection and cardiac allograft vasculopathy. We assessed HLA-G expression in vascular human endothelial and smooth muscle cell cultures to determine if future therapeutic agents can be targeted toward inducing HLA-G expression to protect against allograft rejection and vasculopathy. Methods and Results-Human coronary artery endothelial, aortic endothelial, and coronary artery smooth muscle cell cultures were exposed to cytokines (interferon-␥ or interleukin-10), hypoxia/reoxygenation stress, immunosuppressive agents (cyclosporine, sirolimus, or tacrolimus), or progesterone. HLA-G was not expressed by untreated, normoxic cells. Furthermore, maximal doses of interferon-␥, interleukin-10, cyclosporine, sirolimus, or tacrolimus, as well as exposure to hypoxia/reoxygenation, failed to induce HLA-G expression. HLA-G, which has previously not been detected in adult vascular endothelial and smooth muscle cells, was detected by enzyme-linked immunosorbent assay and flow cytometry in human coronary artery endothelial, human coronary aortic endothelial, and human coronary artery smooth muscle cultures after incubation with progesterone in a dose-dependent manner (PϽ0.001) with no change in cellular proliferation ability or viability. This effect was partially blocked in the presence of mifepristone, a progesterone receptor antagonist (human coronary artery endothelial: 48.8Ϯ15.6%; human coronary aortic endothelial: 59.5Ϯ9.5%; human coronary artery smooth muscle: 59.8Ϯ9.8% of control; PϽ0.05). Progesterone-induced HLA-G expression was not protective against hypoxia/reoxygenation injury. Conclusions-HLA-G is not expressed at baseline in vascular endothelial and smooth muscle cells but can be induced by exposure to progesterone. Although tightly regulated, induction of HLA-G expression in these cells may represent a promising and novel therapeutic strategy to protect against rejection and cardiac allograft vasculopathy after heart transplantation.

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Progesterone enhances HLA-G gene expression in JEG-3 choriocarcinoma cells and human cytotrophoblasts in vitro

Abstract: Progesterone has an up-regulatory effect on HLA-G gene expression in first trimester trophoblasts and JEG-3 cells in vitro.

Cited by 80 publications

References 27 publications

Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy

Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy

RREB-1 Is a Transcriptional Repressor of HLA-G

Progesterone Induces Human Leukocyte Antigen-G Expression in Vascular Endothelial and Smooth Muscle Cells

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