Fractalkine enhances endometrial receptivity and activates iron transport towards trophoblast cells in an in vitro co-culture system of HEC-1A and JEG-3 cells

Pandur, Edina; Pap, Ramóna; Montskó, Gergely; Jánosa, Gergely; Sipos, Katalin; Kovaćs, Gábor L.

doi:10.1016/j.yexcr.2021.112583

Cited by 6 publications

(8 citation statements)

References 72 publications

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“…Maternal body iron status can influence fertility and receptivity and implantation of the embryo (Cerami, 2017; Sangkhae et al, 2020). Iron transport is mediated by the endometrium towards the embryo by specific iron transporters, heme transporters, or extracellular vesicles (Hooda et al, 2014; Nakamura et al, 2020; Pandur et al, 2021). Therefore, iron deficiency in the mother has a deteriorating impact on fetal development causing growth retardation, and abnormal brain maturation (Abu‐Ouf & Jan, 2015; Chavarro et al, 2006; Georgieff, 2020; Kopeć et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

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Regulation of iron metabolism in HEC‐1A endometrium cells by macrophage‐derived factors and fractalkine

Pandur,

Pap,

Jánosa

et al. 2024

Cell Biology International

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Macrophages in the endometrium promote receptivity and implantation by secreting proinflammatory cytokines and other factors like fractalkine (FKN). Macrophages are closely linked to regulating iron homeostasis and can modulate iron availability in the tissue microenvironment. It has been revealed that the iron metabolism of the mother is crucial in fertility. Iron metabolism is strictly controlled by hepcidin, the principal iron regulatory protein. The inflammatory cytokines can modulate hepcidin synthesis and, therefore, the iron metabolism of the endometrium. It was proven recently that FKN, a unique chemokine, is implicated in maternal–fetal communication and may contribute to endometrial receptivity and implantation. In the present study, we investigated the effect of activated THP‐1 macrophages and FKN on the iron metabolism of the HEC‐1A endometrial cells. We established a noncontact coculture with or without recombinant human FKN supplementation to study the impact of the macrophage‐derived factors and FKN on the regulation of hepcidin synthesis and iron release and storage of endometrial cells. Based on our findings, the conditioned medium of the activated macrophages could modify hepcidin synthesis via the nuclear factor kappa‐light‐chain‐enhancer of activated B cells, the signal transducer and activator of transcription 3, and the transferrin receptor 2/bone morphogenetic protein 6/suppressor of mothers against decapentaplegic 1/5/8 signaling pathways, and FKN could alter this effect on the endometrial cells. It was also revealed that the conditioned macrophage medium and FKN modulated the iron release and storage of HEC‐1A cells. FKN signaling may be involved in the management of iron trafficking of the endometrium by the regulation of hepcidin. It can contribute to the iron supply for fetal development at the early stage of the pregnancy.

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Section: Discussionmentioning

confidence: 99%

“…Plasma hepcidin levels are reduced during the second trimester of pregnancy to provide iron to the growing fetus (Nemeth & Ganz, 2023). Before the development of the placenta, the endometrium is responsible for iron transport towards the embryo, in which FP may play a crucial role (Pandur et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Regulation of iron metabolism in HEC‐1A endometrium cells by macrophage‐derived factors and fractalkine

Pandur,

Pap,

Jánosa

et al. 2024

Cell Biology International

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“…Fractalkine is a unique transmembrane molecule expressed by many cells, such as neurons, glial cells immune cells and epithelial cells of the lung, kidneys and intestines and endothelial cells of the blood vessels [ 9 ]. This type of fractalkine, the membrane-bound form, acts as an adhesion molecule for macrophages and leukocytes [ 11 , 14 , 16 ]. The membrane-bound fractalkine can be cleaved by ADAM10 or ADAM17 to produce the soluble form of fractalkine [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…Intracellular total iron measurements were performed according to our previous protocol [ 14 ]. Briefly, THP-1 cells were lysed with 200 µL of 50 mM NaOH at room temperature for 2 h with gentle shaking.…”

Section: Methodsmentioning

confidence: 99%

“…According to the literature, fractalkine (CX3CL1) acts as a chemokine as well as an inflammatory mediator and a regulator of the iron metabolism of various cells [ 8 , 9 , 10 ]. Fractalkine is expressed by many types of cells (e.g., neurons, astrocytes, endometrial cells and immune cells) and is also present on the surface of the endothelial cells of the blood vessels as a membrane-bound form, which provides an anchoring site for the macrophages and lymphocytes [ 11 , 12 , 13 , 14 , 15 , 16 ]. Fractalkine also can be secreted as a soluble form by the proteolytic cleavage of the membrane-bound fractalkine acting as an inflammatory mediator [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Modulatory Effects of Fractalkine on Inflammatory Response and Iron Metabolism of Lipopolysaccharide and Lipoteichoic Acid-Activated THP-1 Macrophages

Pandur

Tamási

Pap

et al. 2022

IJMS

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Fractalkine (CX3CL1) acts as a chemokine as well as a regulator of iron metabolism. Fractalkine binds CX3CR1, the fractalkine receptor on the surface of monocytes/macrophages regulating different intracellular signalling pathways such as mitogen-activated protein kinase (MAPK), phospholipase C (PLC) and NFκB contributing to the production of pro-inflammatory cytokine synthesis, and the regulation of cell growth, differentiation, proliferation and metabolism. In this study, we focused on the modulatory effects of fractalkine on the immune response and on the iron metabolism of Escherichia coli and Pseudomonas aeruginosa lipopolysaccharides (LPS) and Staphylococcus aureus lipoteichoic acid (LTA) activated THP-1 cells to get a deeper insight into the role of soluble fractalkine in the regulation of the innate immune system. Pro-inflammatory cytokine secretions of the fractalkine-treated, LPS/LTA-treated, and co-treated THP-1 cells were determined using ELISArray and ELISA measurements. We analysed the protein expression levels of signalling molecules regulated by CX3CR1 as well as hepcidin, the major iron regulatory hormone, the iron transporters, the iron storage proteins and mitochondrial iron utilization. The results showed that fractalkine treatment alone did not affect the pro-inflammatory cytokine secretion, but it was proposed to act as a regulator of the iron metabolism of THP-1 cells. In the case of two different LPS and one type of LTA with fractalkine co-treatments, fractalkine was able to alter the levels of signalling proteins (NFκB, PSTAT3, Nrf2/Keap-1) regulating the expression of pro-inflammatory cytokines as well as hepcidin, and the iron storage and utilization of the THP-1 cells.

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High glucose and high lipid induced mitochondrial dysfunction in JEG-3 cells through oxidative stress

Yang

Sun

et al. 2023

Open Life Sciences

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Few studies focused on the roles of high glucose combined with high lipid in placental development or fetal growth. This study was designed to investigate the roles of high glucose combined with high lipid in mitochondrial dysfunction of JEG-3 cells. We determined the cellular proliferation and apoptosis, superoxide dismutase (SOD) activity, concentration of malondialdehyde (MDA), and lactic acid dehydrogenase in control group, high glucose group, high lipid group, and high glucose and high lipid group, together with the mitochondrial dysfunction, Nrf2, HO-1, SMAC, and cytochrome C (Cyt-C) expression. Significant decrease of SOD and significant elevation of MDA was seen in high glucose and high lipid group compared with the other three groups. There was significant decrease in mitochondrial SMAC and Cyt-C in high glucose group, high lipid group, and high glucose and high lipid group compared with those of control group. Nrf2 and HO-1 protein expression in high glucose combined with high lipid group showed significant decrease compared with that of high lipid group or high glucose group. We speculated that combination of high glucose and high lipid induced oxidative stress in JEG-3 cells, and Nrf2/ARE pathway may be related to this process.

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Fractalkine enhances endometrial receptivity and activates iron transport towards trophoblast cells in an in vitro co-culture system of HEC-1A and JEG-3 cells

Cited by 6 publications

References 72 publications

Regulation of iron metabolism in HEC‐1A endometrium cells by macrophage‐derived factors and fractalkine

Regulation of iron metabolism in HEC‐1A endometrium cells by macrophage‐derived factors and fractalkine

Modulatory Effects of Fractalkine on Inflammatory Response and Iron Metabolism of Lipopolysaccharide and Lipoteichoic Acid-Activated THP-1 Macrophages

High glucose and high lipid induced mitochondrial dysfunction in JEG-3 cells through oxidative stress

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