TNF-&amp;agr;-Mediated Stress-Induced Early Pregnancy Loss:A Possible Role of Leukemia Inhibitory Factor

Torchinsky, Arkady; Markert, Udo R.; Toder, V.

doi:10.1159/000087913

Cited by 10 publications

(9 citation statements)

References 37 publications

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“…A third possible pathway is through hormone regulation. The elevated estrogen level is associated with pathogenesis of ICP . The disease is more common in multiple than singleton pregnancies (20.9% vs 4.7%) .…”

Section: Discussionmentioning

confidence: 99%

Lithocholic acid‐induced placental tumor necrosis factor‐α upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy

Zhang

Pan

et al. 2013

Hepatology Research

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Section: Discussionmentioning

confidence: 99%

Lithocholic acid‐induced placental tumor necrosis factor‐α upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy

Zhang

Pan

et al. 2013

Hepatology Research

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“…Some results from our work and investigations addressing the functional role of leukemia inhibitory factor (LIF) (see Torchinsky et al, 2005 for references) imply that the cytokine is a good candidate for studies addressing this topic. As to the mechanisms which TNF␣ might engage to act as a teratological protector, convincing evidence suggested that those might be associated with the transcription factor NF-B (see Torchinsky and Toder, 2004 for references).…”

Section: Tnf␣ and Nf-bmentioning

confidence: 91%

Teratogen-induced apoptotic cell death: Does the apoptotic machinery act as a protector of embryos exposed to teratogens?

2005

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Considerable evidence has been collected demonstrating that many teratogens induce apoptotic cell death in embryonic structures that turn out to be malformed in fetuses and newborns. Apoptosis is a genetically regulated process that is realized by the activation of death and pro-survival signaling cascades, and the interplay between these cascades determines whether the cell exposed to apoptotic stimuli dies or survives. Therefore, there is intense interest in understanding how the apoptotic machinery functions in embryos exposed to teratogens. However, the interpretation of the results obtained remains problematic. The main problem is that excessive embryonic cell death, regardless of its nature, if uncompensated for, ultimately leads to maldevelopment or embryonic death. Therefore, we can easily interpret results when the intensity of teratogen-induced cell death and the severity or incidence of teratogen-induced anomalies directly correlate with each other. However, when teratogen-induced cell death is not followed by the formation of anomalies, a usual explanation is that teratogen-induced apoptotic cell death contributes to the renewal of teratogen-targeted cell populations by promoting the removal of injured cells. It is clear that such an explanation leaves vague the role of the anti-apoptotic signaling mechanism (and, hence, the apoptotic machinery as a whole) with respect to protecting the embryo against teratogenic stress. In this review, we summarize the data from studies addressing the function of the apoptotic machinery in embryos exposed to teratogens, and then we discuss approaches to interpreting the results of these studies. We hypothesize that activation of a proapoptotic signaling in teratogen-targeted cell populations is a necessary condition for an anti-apoptotic signaling that counteracts the process of maldevelopment to be activated. If such a scenario is true, we need to modify our approaches to choosing molecular targets for studies addressing this topic.

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“…At high concentrations, TNF can upregulate cell adhesion molecules, disrupt cytoskeletal organization, impair tight junction protein functions, and increase the paracellular permeability of the BBB (Pan et al 1997). Studies in uterine cells have suggested that TNF may affect LIF signaling, and contribute to stress-induced early embryonic death (Torchinsky et al 2005). This raises the questions of whether and how TNF modulates the response of the cerebral endothelial cells to LIF, as both cytokines show increased circulating concentrations in inflammation.…”

Section: Introductionmentioning

confidence: 99%

Opposing effects of proteasomes and lysosomes on LIFR: Modulation by TNF

Kastin

et al. 2007

J Mol Neurosci

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Urocortin, a potent peptide inhibitor of feeding behavior, can enter the brain from blood by leptin-facilitated permeation across the blood-brain barrier. Here, we show in cultured RBE4 cerebral microvessel endothelial cells that urocortin endocytosis is increased by leptin in a time- and dose-dependent manner. Fluorescently labeled urocortin (Alexa488-urocortin) shows vesicular trafficking localized in early endosomes at 1 min and the Golgi complex at 20 min. The endocytosis at 20 min was increased by 10 microg/mL, but not 2 microg/mL, of leptin. The facilitating effect of leptin at the dose of 10 microg/mL was seen at 20 and 30 min but not at 10 min. This increase could be abolished by excess unlabeled urocortin in radio-tracer uptake studies, indicating selective rather than nonsaturable entry. The specificity of the effect was further supported by the lack of changes in gamma-glutamyl transpeptidase activity and endothelial nitric oxide synthase upon stimulation by high doses of leptin and urocortin. Leptin did not affect the level of expression of the urocortin corticotropin-releasing hormone receptor (CRHR) after 30 min of treatment but appeared to slow the turnover of CRHRs induced by urocortin. In MDCK cells overexpressing CRHR2, leptin facilitated urocortin uptake, whereas ObRa coexpression did not exert an additional effect. Thus, urocortin endocytosis is a saturable process leading to vesicular intracellular transport that can be enhanced by cell-surface leptin.

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TNF-&agr;-Mediated Stress-Induced Early Pregnancy Loss:A Possible Role of Leukemia Inhibitory Factor

Abstract: Data presented in the this review suggest LIF as a good candidate for further studies addressing molecular mechanisms underlying stress-induced early embryonic death.

Cited by 10 publications

References 37 publications

Lithocholic acid‐induced placental tumor necrosis factor‐α upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy

Lithocholic acid‐induced placental tumor necrosis factor‐α upregulation and syncytiotrophoblast cell apoptosis in intrahepatic cholestasis of pregnancy

Teratogen-induced apoptotic cell death: Does the apoptotic machinery act as a protector of embryos exposed to teratogens?

Opposing effects of proteasomes and lysosomes on LIFR: Modulation by TNF

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