Localization of Leukemia Inhibitory Factor and Its Receptor in Human Placenta Throughout Pregnancy1

Sharkey, Andrew; King, Ashley; Clark, Dawn E.; Burrows, Tanya D.; Jokhi, Percy; Charnock-Jones, D. Stephen; Loke, Y.W.; Smith, Stephen K.

doi:10.1095/biolreprod60.2.355

Cited by 124 publications

(69 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This finding, together with the finding that LIF stimulates chorionic gonadotrophin production by trophoblast (Sawai et al, 1995), indicates that LIF is an essential mediator between maternal decidua and invading trophoblast (Sharkey et al, 1999).…”

Section: Cytokine Changes With Implantationmentioning

confidence: 73%

Cytokine control in human endometrium

Kelly

King²,

Critchley³

2001

Reproduction

209

View full text Add to dashboard Cite

Critical reproductive events in endometrium such as menstruation and implantation have an inflammatory character (Finn, 1986). Menstruation and implantation involve both prostaglandins and cytokines and are accompanied by the ingress of leucocytes into the endometrium. Moreover, oedema is characteristic of endometrium both premenstrually and at the time of implantation. Endometrial physiology relating to these events is still poorly understood and this ignorance hinders better medical approaches to major pathologies of menstruation, such as menorrhagia and dysmenorrhoea, and failure of implantation.One of the most revealing studies on the mechanism of menstruation was published 60 years ago by Markee (1940) who transplanted endometrium to the anterior chamber of the monkey eye, where events surrounding menstruation could be observed microscopically. The early events of menstruation involve vasoconstriction of the spiral blood vessels followed by a relaxation of the arterioles and reperfusion of the tissue. Prolonged periods of vasoconstriction that would have induced hypoxia and the inevitable reperfusion injury were also observed. Such periods of vasoconstriction have not been confirmed in women in studies with techniques such as Doppler flow (Gannon et al., 1997) and xenon clearance (Fraser et al., 1987), but such techniques are unlikely to detect highly localized changes. Hypoxia would certainly be a sufficient cause of cytokine release since hypoxia affects the NFκB pathway (Royds et al., 1998) and many genes have hypoxic response elements. Re-exposure to oxygen is likely to be accompanied by an upregulation of cytokine (Karakurum et al., 1994) matrix metalloproteinase (MMP) (Fujimura et al., 1999; Heo et al., 1999) vascular endothelial growth factor (VEGF) (Goldberg and Schneider, 1994;Sharkey et al., 2000) and prostaglandin (Kishimoto et al., 1997) production. However, the events preceding vasoconstriction are less clear. The early events in menstruation are initiated by the withdrawal of the circulating progesterone as a result of the demise of the corpus luteum and are likely to involve cells close to the spiral arterioles where the constriction Cytokines within endometrium participate in both menstruation and implantation but also contribute to the defence mechanisms of the mucosal epithelium. Endometrium is under the control of steroid hormones, particularly progesterone and, thus, control of cytokines by this steroid is important. Although appreciable numbers of progesterone receptors are not found in endometrial leucocytes, progesterone can modulate cytokines by acting on uterine cells expressing the receptor. The NFκB pathway is important in the control of cytokine synthesis and can modulate production of chemokines, matrix metalloproteinases and the inducible prostaglandin synthesis enzyme COX-2. NFκB activity can be inhibited by progesterone by either stimulating synthesis of IκB, the molecule that restrains NFκB in the cytosol, or after binding to the nuclear receptor, competing with NFκB for ...

show abstract

Section: Cytokine Changes With Implantationmentioning

confidence: 73%

Cytokine control in human endometrium

Kelly

King²,

Critchley³

2001

Reproduction

209

View full text Add to dashboard Cite

show abstract

“…The presence of LIF and LIFR in decidua and placenta implicates a role not only in implantation, but also in placentation (Kojima et al, 1994, Sharkey et al, 1999. Moreover, LIFR deficient mouse embryos display significant placental defects and growth abnormalities in other organs (Ware et al, 1995).…”

Section: Leukemia Inhibitory Factormentioning

confidence: 99%

Cell signaling in trophoblast-uterine communication

Fritz¹,

Jain²,

Armant³

2014

Int. J. Dev. Biol.

View full text Add to dashboard Cite

Intricate and precise communication between the blastocyst and the uterus orchestrates embryo implantation. However, many questions remain unanswered regarding the molecular complexities of implantation. On-time implantation requires a receptive uterus and a mature blastocyst with trophoblast cells capable of adhering to and invading the endometrium. Defects in uterine receptivity or embryo/uterine signaling can cause implantation failure or early pregnancy loss, whereas deficient trophoblast differentiation can generate placental abnormalities that produce adverse pregnancy outcomes. This review will discuss several examples of signaling pathways that regulate trophoblast and uterine development during this period. Leukemia inhibitory factor is involved in uterine priming for implantation. The epidermal growth factor signaling system contributes to trophoblast-uterine communication, as well as trophoblast adhesion and invasion. Indian hedgehog signaling synchronizes tissue compartments within the uterus, and WNT signaling mediates numerous interactions within the implantation site and developing placenta. The autocrine, paracrine and juxtacrine interactions mediated by these signaling pathways contribute significantly to the establishment of pregnancy, although there are many other known and yet to be discovered factors that synchronize the maternal and embryonic developmental programs.

show abstract

“…34 In the pregnant human uterus, IL-10 is produced in large amounts by both the syncytiotrophoblast and the decidual Mws, 9,10,28,29 while LIF is highly expressed by decidual Mws and uNK cells. 35 On the other hand, the IL-10 receptor is constitutively expressed on placental trophoblasts 28,29 and decidual Mws are known to be highly responsive to IL-10. 9,10 In contrast, the expression level of LIF receptors is significantly higher in both villous and extravillous trophoblasts than in the decidua, 35 suggesting that all cells of the trophoblast lineage are major targets for the action of LIF in the placenta.…”

Section: Introductionmentioning

confidence: 99%

“…35 On the other hand, the IL-10 receptor is constitutively expressed on placental trophoblasts 28,29 and decidual Mws are known to be highly responsive to IL-10. 9,10 In contrast, the expression level of LIF receptors is significantly higher in both villous and extravillous trophoblasts than in the decidua, 35 suggesting that all cells of the trophoblast lineage are major targets for the action of LIF in the placenta. However, the possible interplay between LIF, trophoblast cells and IL-10 in the modulation of Mw functional phenotypes has never been investigated.…”

Section: Introductionmentioning

confidence: 99%

The activating effect of IFN-γ on monocytes/macrophages is regulated by the LIF–trophoblast–IL-10 axis via Stat1 inhibition and Stat3 activation

et al. 2014

View full text Add to dashboard Cite

Interferon gamma (IFN-c) and leukemia inhibitory factor (LIF) are key gestational factors that may differentially affect leukocyte function during gestation. Because IFN-c induces a pro-inflammatory phenotype in macrophages and because trophoblast cells are principal targets of LIF in the placenta, we investigated whether and how soluble factors from trophoblast cells regulate the effects of IFN-c on macrophage activation. IFN-c reduces macrophage motility, but enhances Stat1 activation, pro-inflammatory gene expression and cytotoxic functions. Soluble factors from villous cytotrophoblasts (vCT1LIF cells) and BeWo cells (BW/ST1LIF cells) that were differentiated in the presence of LIF inhibit macrophage Stat1 activation but inversely sustain Stat3 activation in response to IFN-c. vCT1LIF cells produce soluble factors that induce Stat3 activation; this effect is partially abrogated in the presence of neutralizing anti-interleukin 10 (IL-10) antibodies. Moreover, soluble factors from BW/ST1LIF cells reduce cell proliferation but enhance the migratory responses of monocytes. In addition, these factors reverse the inhibitory effect of IFN-c on monocyte/macrophage motility. BW/ST1LIF cells also generate IFN-c-activated macrophages with enhanced IL-10 expression, but reduced tumor-necrosis factor alpha (TNF-a), CD14 and CD40 expression as well as impaired cytotoxic function. Additional assays performed in the presence of neutralizing anti-IL-10 antibodies and exogenous IL-10 demonstrate that reduced macrophage cytotoxicity and proliferation, but increased cell motility result from the ability of trophoblast IL-10 to sustain Stat3 activation and suppress IFN-c-induced Stat1 activation. These in vitro studies are the first to describe the regulatory role of the LIF-trophoblast-IL-10 axis in the process of macrophage activation in response to pro-inflammatory cytokines.

show abstract

Localization of Leukemia Inhibitory Factor and Its Receptor in Human Placenta Throughout Pregnancy1

Cited by 124 publications

References 32 publications

Cytokine control in human endometrium

Cytokine control in human endometrium

Cell signaling in trophoblast-uterine communication

The activating effect of IFN-γ on monocytes/macrophages is regulated by the LIF–trophoblast–IL-10 axis via Stat1 inhibition and Stat3 activation

Contact Info

Product

Resources

About