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)...
Main Authors: | , , , , |
---|---|
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 |
_version_ | 1797474909849387008 |
---|---|
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. |
first_indexed | 2024-03-09T20:37:40Z |
format | Article |
id | doaj.art-2fd7054eadee4e629875de74ff15a4a6 |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-09T20:37:40Z |
publishDate | 2022-02-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
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 |
work_keys_str_mv | AT edinapandur modulatoryeffectsoffractalkineoninflammatoryresponseandironmetabolismoflipopolysaccharideandlipoteichoicacidactivatedthp1macrophages AT kittitamasi modulatoryeffectsoffractalkineoninflammatoryresponseandironmetabolismoflipopolysaccharideandlipoteichoicacidactivatedthp1macrophages AT ramonapap modulatoryeffectsoffractalkineoninflammatoryresponseandironmetabolismoflipopolysaccharideandlipoteichoicacidactivatedthp1macrophages AT gergelyjanosa modulatoryeffectsoffractalkineoninflammatoryresponseandironmetabolismoflipopolysaccharideandlipoteichoicacidactivatedthp1macrophages AT katalinsipos modulatoryeffectsoffractalkineoninflammatoryresponseandironmetabolismoflipopolysaccharideandlipoteichoicacidactivatedthp1macrophages |