The role of interleukin-6 in redox homeostasis and migration capacity in human trophoblast cells JEG-3 under condition of chemically induced hypoxia

Background/Aims: The placenta is a vital organ for pregnancy. Many in vitro placental experiments are conducted under 21% O2; however, O2 tension could influence cellular functions, including cytokine secretion. We investigated the effects of oxygen tension between moderate hypoxia (5% O2) and normoxia (21% O2) by testing the hypothesis that moderate hypoxia regulates cellular phenotypes differently from normoxia in human trophoblast cells. Methods and Results: Sw.71 trophoblast cells were incubated under normoxic or moderately hypoxic conditions. Cells were also treated with lipopolysaccharide (LPS) as a Toll-like receptor 4 (TLR4) ligand inducing inflammation. Interleukin-6 (IL-6) as an inflammatory cytokine was determined, and TLR4, hypoxia-induced factor-1α (HIF1α), and reactive oxygen species (ROS) production were detected. Moderate hypoxia increased HIF1α expression and cell proliferation and acted by two different mechanisms to decrease IL-6 secretion compared with normoxia: it limits the TLR4 expression and ROS production. Treatment with cobalt chloride as an HIF1 activator inhibited IL-6 secretion and TLR4 expression; this effect was reversed on treatment with PX-12 as an HIF1 suppressor. Conclusion: IL-6 secretion, TLR4 expression, and ROS production, classical markers of inflammation, are down-regulated by moderate hypoxia, and HIF1α and ROS have a potential to regulate these responses in human trophoblast cells.

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The role of SDF2 (Stromal cell derived factor 2) in Cell Survival/Death Decision during Endoplasmic Reticulum Stress in Human Trophoblast cells

Placenta ◽

10.1016/j.placenta.2017.07.116 ◽

2017 ◽

Vol 57 ◽

pp. 257

Author(s):

Aline R. Lorenzon-Ojea ◽

Clarissa Ribeiro Rocha ◽

Estela Bevilacqua

Keyword(s):

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Cell Survival ◽

Stromal Cell ◽

Trophoblast Cells ◽

Human Trophoblast ◽

Stromal Cell Derived Factor ◽

Human Trophoblast Cells

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New insights into the function of Cullin 3 in trophoblast invasion and migration

Reproduction ◽

10.1530/rep-15-0126 ◽

2015 ◽

Vol 150 (2) ◽

pp. 139-149 ◽

Cited By ~ 9

Author(s):

Qian Zhang ◽

Song Yu ◽

Xing Huang ◽

Yi Tan ◽

Cheng Zhu ◽

...

Keyword(s):

Ex Vivo ◽

Trophoblast Invasion ◽

Trophoblast Cells ◽

Human Trophoblast ◽

Invasion And Migration ◽

Cullin 3 ◽

And Migration ◽

F Box Protein ◽

Extravillous Trophoblasts

Cullin 3 (CUL3), a scaffold protein, assembles a large number of ubiquitin ligase complexes, similar to Skp1-Cullin 1-F-box protein complex. Several genetic models have shown that CUL3 is crucial for early embryonic development. Nevertheless, the role of CUL3 in human trophoblast function remains unclear. In this study, immunostaining revealed that CUL3 was strongly expressed in the villous cytotrophoblasts, the trophoblast column, and the invasive extravillous trophoblasts. Silencing CUL3 significantly inhibited the outgrowth of villous explant ex vivo and decreased invasion and migration of trophoblast HTR8/SVneo cells. Furthermore, CUL3 siRNA decreased pro-MMP9 activity and increased the levels of TIMP1 and 2. We also found that the level of CUL3 in the placental villi from pre-eclamptic patients was significantly lower as compared to that from their gestational age-matched controls. Moreover, in the lentiviral-mediated placenta-specific CUL3 knockdown mice, lack of CUL3 resulted in less invasive trophoblast cells in the maternal decidua. Taken together, these results suggest an essential role for CUL3 in the invasion and migration of trophoblast cells, and dysregulation of its expression may be associated with the onset of pre-eclampsia.

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Localization of Nitric Oxide Synthase in Human Trophoblast Cells: Role of Nitric Oxide in Trophoblast Proliferation and Differentiation

American Journal of Reproductive Immunology ◽

10.1111/j.8755-8920.2000.430202.x ◽

2000 ◽

Vol 43 (2) ◽

pp. 70-77 ◽

Cited By ~ 20

Author(s):

CHANDANA DAS ◽

MRINMOY SANYAL ◽

TAPAS CHANDRA NAG

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Trophoblast Cells ◽

Human Trophoblast ◽

Proliferation And Differentiation ◽

Oxide Synthase ◽

Human Trophoblast Cells

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Decorin-Mediated Inhibition of Human Trophoblast Cells Proliferation, Migration, and Invasion and Promotion of ApoptosisIn Vitro

BioMed Research International ◽

10.1155/2015/201629 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Yanfen Zou ◽

Xiang Yu ◽

Jing Lu ◽

Ziyan Jiang ◽

Qing Zuo ◽

...

Keyword(s):

Inhibitory Effect ◽

Extravillous Trophoblast ◽

Migration And Invasion ◽

Trophoblast Cells ◽

Human Trophoblast ◽

The Matrix ◽

Polymerase Chain ◽

And Migration ◽

Human Trophoblast Cells

Preeclampsia (PE) is a unique complication of pregnancy, the pathogenesis of which has been generally accepted to be associated with the dysfunctions of extravillous trophoblast (EVT) including proliferation, apoptosis, and migration and invasion. Decorin (DCN) has been proved to be a decidua-derived TGF-binding proteoglycan, which negatively regulates proliferation, migration, and invasiveness of human extravillous trophoblast cells. In this study, we identified a higher expression level of decorin in severe PE placentas by both real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). And an inhibitory effect of decorin on proliferation, migration, and invasion and an enhanced effect on apoptosis in trophoblast cells HTR-8/SVneo and JEG-3 were validatedin vitro. Also the modulations of decorin on trophoblast cells’ metastasis and invasion functions were detected through regulating the matrix metalloproteinases (MMP2 and MMP9). Thus, we suggested that the contribution of decorin to the modulation of trophoblast cells might have implications for the pathogenesis of preeclampsia.

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