ORIGINAL ARTICLE: HLA‐G Expression Is Up‐Regulated by Progesterone in Mesenchymal Stem Cells

Ivanova‐Todorova, Ekaterina; Mourdjeva, Milena; Kyurkchiev, Dobroslav; Bochev, Ivan; Stoyanova, Elena; Dimitrov, Rumen; Timeva, Tanya; Yunakova, Maria; Bukarev, Dimitar; Shterev, A; Tivchev, Petar; Kyurkchiev, Stanimir

doi:10.1111/j.1600-0897.2009.00707.x

Cited by 41 publications

(28 citation statements)

References 39 publications

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“…Similarly, increased HLA-G expression has been observed in human cytotrophoblast cells, JEG-3 chorioncarcinoma cells [34], and mesenchymal stem cells [89] in response to exposure to P4. Subsequently, it was revealed that HLA-G gene expression is upregulated by P4 through the nuclear progesterone receptor (nPRG) complex binding to a unique PRE sequence in the promoter region of the HLA-G gene that showed 60% homology to the wild type mouse mammary tumor virus (MMTV) PRE [90].…”

Section: Discussionmentioning

confidence: 92%

Regulation of a Bovine Nonclassical Major Histocompatibility Complex Class I Gene Promoter1

O'Gorman

Naib²,

Ellis

et al. 2010

Biology of Reproduction

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Studies have shown in humans and other species that the major histocompatibility complex class I (MHC-I) region is involved at a number of levels in the establishment and maintenance of pregnancy. The aim of this study was to characterize how a bovine nonclassical MHC-I gene (NC1) is regulated. Initial serial deletion experiments of a 2-kb fragment of the NC1 promoter identified regions with positive regulatory elements in the proximal promoter and evidence for a silencer module(s) further upstream that cooperatively contributed to constitutive NC1 expression. The cytokines interferon tau (IFNT), interferon gamma (IFNG), and interleukin 4 (IL4) significantly increased luciferase expression in NC1 promoter reporter constructs and endogenous NC1 mRNA levels in a bovine endometrial cell line. In addition, IFNG, IL3, IL4, and progesterone significantly increased Day 7 bovine blastocyst NC1 mRNA expression when supplemented during in vitro embryo culture. Site-directed mutagenesis analysis identified a STAT6 binding site that conferred IL4 responsiveness in the NC1 proximal promoter. Furthermore, methylation treatment of the proximal promoter, which contains a CpG island, completely abrogated constitutive NC1 expression. Overall, the findings presented here suggest that constitutive NC1 expression is regulated positively by elements in the proximal promoter, which are further controlled by upstream silencer modules. The promoter is responsive to IFNT, IFNG, and IL4, suggesting possible roles for these cytokines in bovine preimplantation embryo survival and/or maternal-fetal tolerance. Our studies also suggest that methylation of the proximal promoter, in particular, could play a significant role in regulating NC1 expression.

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Section: Discussionmentioning

confidence: 92%

Regulation of a Bovine Nonclassical Major Histocompatibility Complex Class I Gene Promoter1

O'Gorman

Naib²,

Ellis

et al. 2010

Biology of Reproduction

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“…This expression can be up-regulated by progesterone treatment (75) and pro-inflammatory cytokines (76). Furthermore, the induction of HLA-G expression as a strategy to enhance the immunosuppressive properties of MSC in transplantation has been postulated (77).…”

Section: Molecular Mechanisms Of Msc Immunosuppressive Effectmentioning

confidence: 99%

Innate Immune System and Preeclampsia

et al. 2014

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Normal pregnancy is considered as a Th2 type immunological state that favors an immune-tolerance environment in order to prevent fetal rejection. Preeclampsia (PE) has been classically described as a Th1/Th2 imbalance; however, the Th1/Th2 paradigm has proven insufficient to fully explain the functional and molecular changes observed during normal/pathological pregnancies. Recent studies have expanded the Th1/Th2 into a Th1/Th2/Th17 and regulatory T-cells paradigm and where dendritic cells could have a crucial role. Recently, some evidence has emerged supporting the idea that mesenchymal stem cells might be part of the feto-maternal tolerance environment. This review will discuss the involvement of the innate immune system in the establishment of a physiological environment that favors pregnancy and possible alterations related to the development of PE.

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“…Recently, data have shon that MSCs deriving either from adipose tissue or from deciduas or from cord blood were able to express HLA-G molecules [98]. A study using cord blood-derived MSCs also showed that cells were able to secrete HLA-G even if MSCs were expanded in vitro within medium containing 5% platelet lysate used as a substitute for calf serum [99].…”

Section: Mesenchymal Stem Cells Secreting Hla-gmentioning

confidence: 96%

HLA-G in organ transplantation: towards clinical applications

Deschaseaux

Delgado

Pistoia

et al. 2010

Cell. Mol. Life Sci.

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HLA-G plays a particular role during pregnancy in which its expression at the feto-maternal barrier participates into the tolerance of the allogenic foetus. HLA-G has also been demonstrated to be expressed in some transplanted patients, suggesting that it regulates the allogenic response. In vitro data indicate that HLA-G modulates NK cells, T cells, and DC maturation through its interactions with various inhibitory receptors. In this paper, we will review the data reporting the HLA-G involvement of HLA-G in human organ transplantation, then factors that can modulate HLA-G, and finally the use of HLA-G as a therapeutic tool in organ transplantation.

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ORIGINAL ARTICLE: HLA‐G Expression Is Up‐Regulated by Progesterone in Mesenchymal Stem Cells

Abstract: Progesterone up-regulates the expression by MSCs of HLA-G which is a major player in maintenance of the immune balance between the mother and the fetus. MSCs are newly detected targets of progesterone with well documented immunomodulatory activity.

Cited by 41 publications

References 39 publications

Regulation of a Bovine Nonclassical Major Histocompatibility Complex Class I Gene Promoter1

Regulation of a Bovine Nonclassical Major Histocompatibility Complex Class I Gene Promoter1

Innate Immune System and Preeclampsia

HLA-G in organ transplantation: towards clinical applications

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