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Placental CX3CL1 is Deregulated by Angiotensin II and Contributes to a Pro-Inflammatory Trophoblast-Monocyte Interaction
CX3CL1, which is a chemokine involved in many aspects of human pregnancy, is a membrane-bound chemokine shed into circulation as a soluble isoform. Placental CX3CL1 is induced by inflammatory cytokines and is upregulated in severe early-onset preeclampsia. In this study, the hypothesis was addressed...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387455/ https://www.ncbi.nlm.nih.gov/pubmed/30717334 http://dx.doi.org/10.3390/ijms20030641 |
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author | Nonn, Olivia Güttler, Jacqueline Forstner, Désirée Maninger, Sabine Zadora, Julianna Balogh, András Frolova, Alina Glasner, Andreas Herse, Florian Gauster, Martin |
author_facet | Nonn, Olivia Güttler, Jacqueline Forstner, Désirée Maninger, Sabine Zadora, Julianna Balogh, András Frolova, Alina Glasner, Andreas Herse, Florian Gauster, Martin |
author_sort | Nonn, Olivia |
collection | PubMed |
description | CX3CL1, which is a chemokine involved in many aspects of human pregnancy, is a membrane-bound chemokine shed into circulation as a soluble isoform. Placental CX3CL1 is induced by inflammatory cytokines and is upregulated in severe early-onset preeclampsia. In this study, the hypothesis was addressed whether angiotensin II can deregulate placental CX3CL1 expression, and whether CX3CL1 can promote a pro-inflammatory status of monocytes. qPCR analysis of human placenta samples (n = 45) showed stable expression of CX3CL1 and the angiotensin II receptor AGTR1 throughout the first trimester, but did not show a correlation between both or any influence of maternal age, BMI, and gestational age. Angiotensin II incubation of placental explants transiently deregulated CX3CL1 expression, while the angiotensin II receptor antagonist candesartan reversed this effect. Overexpression of recombinant human CX3CL1 in SGHPL-4 trophoblasts increased adhesion of THP-1 monocytes and significantly increased IL8, CCL19, and CCL13 in co-cultures with human primary monocytes. Incubation of primary monocytes with CX3CL1 and subsequent global transcriptome analysis of CD16(+) subsets revealed 81 upregulated genes, including clusterin, lipocalin-2, and the leptin receptor. Aldosterone synthase, osteopontin, and cortisone reductase were some of the 66 downregulated genes present. These data suggest that maternal angiotensin II levels influence placental CX3CL1 expression, which, in turn, can affect monocyte to trophoblast adhesion. Release of placental CX3CL1 could promote the pro-inflammatory status of the CD16(+) subset of maternal monocytes. |
format | Online Article Text |
id | pubmed-6387455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63874552019-02-27 Placental CX3CL1 is Deregulated by Angiotensin II and Contributes to a Pro-Inflammatory Trophoblast-Monocyte Interaction Nonn, Olivia Güttler, Jacqueline Forstner, Désirée Maninger, Sabine Zadora, Julianna Balogh, András Frolova, Alina Glasner, Andreas Herse, Florian Gauster, Martin Int J Mol Sci Article CX3CL1, which is a chemokine involved in many aspects of human pregnancy, is a membrane-bound chemokine shed into circulation as a soluble isoform. Placental CX3CL1 is induced by inflammatory cytokines and is upregulated in severe early-onset preeclampsia. In this study, the hypothesis was addressed whether angiotensin II can deregulate placental CX3CL1 expression, and whether CX3CL1 can promote a pro-inflammatory status of monocytes. qPCR analysis of human placenta samples (n = 45) showed stable expression of CX3CL1 and the angiotensin II receptor AGTR1 throughout the first trimester, but did not show a correlation between both or any influence of maternal age, BMI, and gestational age. Angiotensin II incubation of placental explants transiently deregulated CX3CL1 expression, while the angiotensin II receptor antagonist candesartan reversed this effect. Overexpression of recombinant human CX3CL1 in SGHPL-4 trophoblasts increased adhesion of THP-1 monocytes and significantly increased IL8, CCL19, and CCL13 in co-cultures with human primary monocytes. Incubation of primary monocytes with CX3CL1 and subsequent global transcriptome analysis of CD16(+) subsets revealed 81 upregulated genes, including clusterin, lipocalin-2, and the leptin receptor. Aldosterone synthase, osteopontin, and cortisone reductase were some of the 66 downregulated genes present. These data suggest that maternal angiotensin II levels influence placental CX3CL1 expression, which, in turn, can affect monocyte to trophoblast adhesion. Release of placental CX3CL1 could promote the pro-inflammatory status of the CD16(+) subset of maternal monocytes. MDPI 2019-02-02 /pmc/articles/PMC6387455/ /pubmed/30717334 http://dx.doi.org/10.3390/ijms20030641 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nonn, Olivia Güttler, Jacqueline Forstner, Désirée Maninger, Sabine Zadora, Julianna Balogh, András Frolova, Alina Glasner, Andreas Herse, Florian Gauster, Martin Placental CX3CL1 is Deregulated by Angiotensin II and Contributes to a Pro-Inflammatory Trophoblast-Monocyte Interaction |
title | Placental CX3CL1 is Deregulated by Angiotensin II and Contributes to a Pro-Inflammatory Trophoblast-Monocyte Interaction |
title_full | Placental CX3CL1 is Deregulated by Angiotensin II and Contributes to a Pro-Inflammatory Trophoblast-Monocyte Interaction |
title_fullStr | Placental CX3CL1 is Deregulated by Angiotensin II and Contributes to a Pro-Inflammatory Trophoblast-Monocyte Interaction |
title_full_unstemmed | Placental CX3CL1 is Deregulated by Angiotensin II and Contributes to a Pro-Inflammatory Trophoblast-Monocyte Interaction |
title_short | Placental CX3CL1 is Deregulated by Angiotensin II and Contributes to a Pro-Inflammatory Trophoblast-Monocyte Interaction |
title_sort | placental cx3cl1 is deregulated by angiotensin ii and contributes to a pro-inflammatory trophoblast-monocyte interaction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387455/ https://www.ncbi.nlm.nih.gov/pubmed/30717334 http://dx.doi.org/10.3390/ijms20030641 |
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