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

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)...

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Main Authors: Edina Pandur, Kitti Tamási, Ramóna Pap, Gergely Jánosa, Katalin Sipos
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/5/2629
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author Edina Pandur
Kitti Tamási
Ramóna Pap
Gergely Jánosa
Katalin Sipos
author_facet Edina Pandur
Kitti Tamási
Ramóna Pap
Gergely Jánosa
Katalin Sipos
author_sort Edina Pandur
collection DOAJ
description 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 <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> lipopolysaccharides (LPS) and <i>Staphylococcus aureus</i> 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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spelling doaj.art-2fd7054eadee4e629875de74ff15a4a62023-11-23T23:07:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01235262910.3390/ijms23052629Modulatory Effects of Fractalkine on Inflammatory Response and Iron Metabolism of Lipopolysaccharide and Lipoteichoic Acid-Activated THP-1 MacrophagesEdina Pandur0Kitti Tamási1Ramóna Pap2Gergely Jánosa3Katalin Sipos4Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Pécs, Rókus Str. 2, H-7624 Pécs, HungaryDepartment of Pharmaceutical Biology, Faculty of Pharmacy, University of Pécs, Rókus Str. 2, H-7624 Pécs, HungaryDepartment of Pharmaceutical Biology, Faculty of Pharmacy, University of Pécs, Rókus Str. 2, H-7624 Pécs, HungaryDepartment of Pharmaceutical Biology, Faculty of Pharmacy, University of Pécs, Rókus Str. 2, H-7624 Pécs, HungaryDepartment of Pharmaceutical Biology, Faculty of Pharmacy, University of Pécs, Rókus Str. 2, H-7624 Pécs, HungaryFractalkine (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 <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> lipopolysaccharides (LPS) and <i>Staphylococcus aureus</i> 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.https://www.mdpi.com/1422-0067/23/5/2629macrophagefractalkineinflammationiron metabolismcell signallingcytokine
spellingShingle Edina Pandur
Kitti Tamási
Ramóna Pap
Gergely Jánosa
Katalin Sipos
Modulatory Effects of Fractalkine on Inflammatory Response and Iron Metabolism of Lipopolysaccharide and Lipoteichoic Acid-Activated THP-1 Macrophages
International Journal of Molecular Sciences
macrophage
fractalkine
inflammation
iron metabolism
cell signalling
cytokine
title Modulatory Effects of Fractalkine on Inflammatory Response and Iron Metabolism of Lipopolysaccharide and Lipoteichoic Acid-Activated THP-1 Macrophages
title_full Modulatory Effects of Fractalkine on Inflammatory Response and Iron Metabolism of Lipopolysaccharide and Lipoteichoic Acid-Activated THP-1 Macrophages
title_fullStr Modulatory Effects of Fractalkine on Inflammatory Response and Iron Metabolism of Lipopolysaccharide and Lipoteichoic Acid-Activated THP-1 Macrophages
title_full_unstemmed Modulatory Effects of Fractalkine on Inflammatory Response and Iron Metabolism of Lipopolysaccharide and Lipoteichoic Acid-Activated THP-1 Macrophages
title_short Modulatory Effects of Fractalkine on Inflammatory Response and Iron Metabolism of Lipopolysaccharide and Lipoteichoic Acid-Activated THP-1 Macrophages
title_sort modulatory effects of fractalkine on inflammatory response and iron metabolism of lipopolysaccharide and lipoteichoic acid activated thp 1 macrophages
topic macrophage
fractalkine
inflammation
iron metabolism
cell signalling
cytokine
url https://www.mdpi.com/1422-0067/23/5/2629
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