Interleukin-17A Triggers the Release of Platelet-Derived Factors Driving Vascular Endothelial Cells toward a Pro-Angiogenic State
Platelets comprise a highly interactive immune cell subset of the circulatory system traditionally known for their unique haemostatic properties. Although platelets are considered as a vault of growth factors, cytokines and chemokines with pivotal role in vascular regeneration and angiogenesis, the...
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MDPI AG
2021-07-01
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author | Aikaterini Gatsiou Kateryna Sopova Alexandros Tselepis Konstantinos Stellos |
author_facet | Aikaterini Gatsiou Kateryna Sopova Alexandros Tselepis Konstantinos Stellos |
author_sort | Aikaterini Gatsiou |
collection | DOAJ |
description | Platelets comprise a highly interactive immune cell subset of the circulatory system traditionally known for their unique haemostatic properties. Although platelets are considered as a vault of growth factors, cytokines and chemokines with pivotal role in vascular regeneration and angiogenesis, the exact mechanisms by which they influence vascular endothelial cells (ECs) function remain underappreciated. In the present study, we examined the role of human IL-17A/IL-17RA axis in platelet-mediated pro-angiogenic responses. We reveal that IL-17A receptor (IL-17RA) mRNA is present in platelets transcriptome and a profound increase is documented on the surface of activated platelets. By quantifying the protein levels of several factors, involved in angiogenesis, we identified that IL-17A/IL17RA axis selectively induces the release of vascular endothelial growth factor, interleukin -2 and -4, as well as monocyte chemoattractant protein -1 from treated platelets. However, IL-17A exerted no effect on the release of IL-10, an anti-inflammatory factor with potentially anti-angiogenic properties, from platelets. Treatment of human endothelial cell two-dimensional tubule networks or three-dimensional spheroid and mouse aortic ring structures with IL-17A-induced platelet releasate evoked pro-angiogenic responses of ECs. Our findings suggest that IL-17A may critically affect platelet release of pro-angiogenic factors driving ECs towards a pro-angiogenic state. |
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format | Article |
id | doaj.art-272c73a4427845b48004e0be12319845 |
institution | Directory Open Access Journal |
issn | 2073-4409 |
language | English |
last_indexed | 2024-03-10T08:55:17Z |
publishDate | 2021-07-01 |
publisher | MDPI AG |
record_format | Article |
series | Cells |
spelling | doaj.art-272c73a4427845b48004e0be123198452023-11-22T07:08:16ZengMDPI AGCells2073-44092021-07-01108185510.3390/cells10081855Interleukin-17A Triggers the Release of Platelet-Derived Factors Driving Vascular Endothelial Cells toward a Pro-Angiogenic StateAikaterini Gatsiou0Kateryna Sopova1Alexandros Tselepis2Konstantinos Stellos3RNA Metabolism and Vascular Inflammation Group, Center of Molecular Medicine, Institute of Cardiovascular Regeneration, Johann Wolfgang Goethe University, 60596 Frankfurt am Main, GermanyRNA Metabolism and Vascular Inflammation Group, Center of Molecular Medicine, Institute of Cardiovascular Regeneration, Johann Wolfgang Goethe University, 60596 Frankfurt am Main, GermanyLaboratory of Clinical Biochemistry, Atherothrombosis Research Center, University of Ioannina, 45110 Ioannina, GreeceRNA Metabolism and Vascular Inflammation Group, Center of Molecular Medicine, Institute of Cardiovascular Regeneration, Johann Wolfgang Goethe University, 60596 Frankfurt am Main, GermanyPlatelets comprise a highly interactive immune cell subset of the circulatory system traditionally known for their unique haemostatic properties. Although platelets are considered as a vault of growth factors, cytokines and chemokines with pivotal role in vascular regeneration and angiogenesis, the exact mechanisms by which they influence vascular endothelial cells (ECs) function remain underappreciated. In the present study, we examined the role of human IL-17A/IL-17RA axis in platelet-mediated pro-angiogenic responses. We reveal that IL-17A receptor (IL-17RA) mRNA is present in platelets transcriptome and a profound increase is documented on the surface of activated platelets. By quantifying the protein levels of several factors, involved in angiogenesis, we identified that IL-17A/IL17RA axis selectively induces the release of vascular endothelial growth factor, interleukin -2 and -4, as well as monocyte chemoattractant protein -1 from treated platelets. However, IL-17A exerted no effect on the release of IL-10, an anti-inflammatory factor with potentially anti-angiogenic properties, from platelets. Treatment of human endothelial cell two-dimensional tubule networks or three-dimensional spheroid and mouse aortic ring structures with IL-17A-induced platelet releasate evoked pro-angiogenic responses of ECs. Our findings suggest that IL-17A may critically affect platelet release of pro-angiogenic factors driving ECs towards a pro-angiogenic state.https://www.mdpi.com/2073-4409/10/8/1855IL-17Aplateletsendothelial cellsangiogenesissproutingVEGF |
spellingShingle | Aikaterini Gatsiou Kateryna Sopova Alexandros Tselepis Konstantinos Stellos Interleukin-17A Triggers the Release of Platelet-Derived Factors Driving Vascular Endothelial Cells toward a Pro-Angiogenic State Cells IL-17A platelets endothelial cells angiogenesis sprouting VEGF |
title | Interleukin-17A Triggers the Release of Platelet-Derived Factors Driving Vascular Endothelial Cells toward a Pro-Angiogenic State |
title_full | Interleukin-17A Triggers the Release of Platelet-Derived Factors Driving Vascular Endothelial Cells toward a Pro-Angiogenic State |
title_fullStr | Interleukin-17A Triggers the Release of Platelet-Derived Factors Driving Vascular Endothelial Cells toward a Pro-Angiogenic State |
title_full_unstemmed | Interleukin-17A Triggers the Release of Platelet-Derived Factors Driving Vascular Endothelial Cells toward a Pro-Angiogenic State |
title_short | Interleukin-17A Triggers the Release of Platelet-Derived Factors Driving Vascular Endothelial Cells toward a Pro-Angiogenic State |
title_sort | interleukin 17a triggers the release of platelet derived factors driving vascular endothelial cells toward a pro angiogenic state |
topic | IL-17A platelets endothelial cells angiogenesis sprouting VEGF |
url | https://www.mdpi.com/2073-4409/10/8/1855 |
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