IL-6, TNFα and TGFβ Promote Nonapoptotic Trophoblast Deportation and Subsequently Causes Endothelial Cell Activation

Chen, L.M.; Liu, Bonnia; Zhao, Hongbo; Stone, Peter; Chen, Q.; Chamley, Larry

doi:10.1016/j.placenta.2009.11.005

Cited by 78 publications

(41 citation statements)

References 17 publications

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“…Other studies have demonstrated high levels of production of IL6 by BeWo cells and its involvement in the endocrine properties of these cells [22,72]. However, this cytokine should be at adequate concentrations at the maternal-fetal interface because high levels of IL6 are associated with preeclampsia and inflammatory processes in the amnion [73,74]. Thus, it is plausible that TGFB1 and IL10 down-modulate IL6 release in order to control the level of this cytokine in BeWo cells, which in turn, promotes the increased proliferation of T. gondii, allowing dissemination of the infection in our model.…”

Section: Discussionmentioning

confidence: 98%

IL10, TGF Beta1, and IFN Gamma Modulate Intracellular Signaling Pathways and Cytokine Production to Control Toxoplasma gondii Infection in BeWo Trophoblast Cells1

Barbosa

Lopes-Maria

Gomes

et al. 2015

Biology of Reproduction

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Considering that interleukin 10 (IL10), transforming growth factor beta1 (TGFB1), and interferon gamma (IFNG) are involved in the susceptibility of BeWo trophoblast cells to Toxoplasma gondii infection, the aim of the present study was to investigate the effector mechanisms triggered by these cytokines in the control of T. gondii in BeWo cells. For this purpose, infected/uninfected BeWo cells were treated with IL10, TGFB1 (50 ng/ml), and IFNG (20 or 100 ng/ml) in order to verify the phosphorylation of signal transducers and activators of transcription 1 (STAT1), STAT3, and Smad2, parasite intracellular proliferation, as well as the Th1/Th2/IL17A cytokine production. The treatment of BeWo cells with IL10 and TGFB1 favored T. gondii proliferation, and these findings were associated with STAT3 and Smad2 phosphorylation, respectively (P < 0.05). Also, these cytokine treatments were able to down-modulate TNF alpha (TNFA) and IL6 production (P < 0.05). Low concentration of IFNG was unable to control T. gondii infection but was able to trigger STAT1 phosphorylation and up-regulate IL6 and IL17A production; whereas a high concentration of IFNG was unable to activate STAT1 but down-modulated IL6 and TNFA and increased T. gondii proliferation (P < 0.05). IL10, TGFB1, and IFNG regulate a differential T. gondii proliferation in BeWo cells because they distinctly trigger intracellular signaling pathways and cytokine production, especially IL6 and TNFA. Our data open new windows to understand the mechanisms triggered by IL10, TGFB1, and IFNG at the maternal-fetal interface in the presence of T. gondii, contributing to recognizing the importance of these effector mechanisms involved in the vertical transmission of this parasite.

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Section: Discussionmentioning

confidence: 98%

IL10, TGF Beta1, and IFN Gamma Modulate Intracellular Signaling Pathways and Cytokine Production to Control Toxoplasma gondii Infection in BeWo Trophoblast Cells1

Barbosa

Lopes-Maria

Gomes

et al. 2015

Biology of Reproduction

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“…The possible triggers for releasing STBEVs are currently not known, nor why some are shed by blebbing and some released by exocytosisdriven mechanisms. Whether regulated exocytosis release is triggered by calcium in the placenta has not been investigated, although a role for calcium-triggered release of exosomes has been shown in other cell types (Soo et al 2012) and various cytokines can also increase non-apoptotic trophoblast deportation from placental explants (Chen et al 2010). Interestingly, we have shown that calmodulin 2 is significantly downregulated in PE placentae (Centlow et al 2008).…”

Section: Sources Of Stbevs and Isolation Methodsmentioning

confidence: 99%

Placenta-derived extracellular vesicles: their cargo and possible functions

Familari

Cronqvist

Masoumi

et al. 2017

Reprod. Fertil. Dev.

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The literature on extracellular vesicles consists of rapidly expanding and often contradictory information. In this paper we attempt to review what is currently known regarding extracellular vesicles released specifically from human placental syncytiotrophoblast cells with a focus on the common but complex pregnancy-associated syndrome pre-eclampsia, where the level of syncytiotrophoblast extracellular vesicle release is significantly increased. We review common methods for syncytiotrophoblast extracellular vesicle derivation and isolation and we discuss the cargo of syncytiotrophoblast extracellular vesicles including proteins, RNA and lipids and their possible functions. A meta-analysis of available trophoblast-derived extracellular vesicle proteomic datasets revealed only three proteins in common: albumin, fibronectin-1 and plasminogen activator inhibitor-1, suggesting some variability in vesicle cargo, most likely reflecting stage and cell type of origin. We discuss the possible sources of variability that may have led to the low number of common markers, which has led us to speculate that markers and density in common use may not be strict criteria for identifying and isolating placenta-derived exosomes.

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“…Placental increases in TNF-α and IL-6, as seen during PE, have been shown to excessively increase the death of trophoblast cells and increase endothelial activation (82). Ultimately, these inflammatory cytokines lead to endothelial dysfunction and the vasoconstrictor, endothelin-1, ROS and decreased NO which contribute to the hypertension present during PE (83, 84).…”

Section: Pathophysiology Of Preeclampsiamentioning

confidence: 99%

The role of inflammation in the pathology of preeclampsia

et al. 2016

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Preeclampsia (PE) affects 5–7% of all pregnancies in the U.S. and is the leading cause of maternal and prenatal morbidity. PE is associated with hypertension after week 20 of gestation, decreased renal function, and small-for-gestational-age babies. Women with PE exhibit chronic inflammation and production of autoantibodies. It is hypothesized that during PE, placental ischemia occurs as a result of shallow trophoblast invasion which is associated with an immune imbalance where pro-inflammatory CD4+ T cells are increased and T regulatory cells (Tregs) are decreased. This imbalance leads to chronic inflammation characterized by oxidative stress, pro-inflammatory cytokines, and autoantibodies. Studies conducted in our laboratory have demonstrated the importance of this immune imbalance to cause hypertension in response to placental ischemia in pregnant rats. These studies confirm that increased CD4+ T cells and decreased Tregs during pregnancy leads to elevated inflammatory cytokines, endothelin (ET-1), reactive oxygen species (ROS), and agonistic autoantibodies to the Angiotensin II (Ang II), type 1 receptor (AT1-AA). All of these factors taken together play an important role in increasing the blood pressure during pregnancy. Specifically, this review focuses on the decrease in Tregs, and their associated regulatory cytokine IL-10, which is seen in response to placental ischemia during pregnancy. This study will also examine the effect of regulatory immune cell repopulation on the pathophysiology of preeclampsia. These studies show that restoring the balance of the immune system through increasing Tregs, either by adoptive transfer or by infusing IL-10, reduces the blood pressure and pathophysiology associated with placental ischemia in pregnant rats.

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IL-6, TNFα and TGFβ Promote Nonapoptotic Trophoblast Deportation and Subsequently Causes Endothelial Cell Activation

Cited by 78 publications

References 17 publications

IL10, TGF Beta1, and IFN Gamma Modulate Intracellular Signaling Pathways and Cytokine Production to Control Toxoplasma gondii Infection in BeWo Trophoblast Cells1

IL10, TGF Beta1, and IFN Gamma Modulate Intracellular Signaling Pathways and Cytokine Production to Control Toxoplasma gondii Infection in BeWo Trophoblast Cells1

Placenta-derived extracellular vesicles: their cargo and possible functions

The role of inflammation in the pathology of preeclampsia

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