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PAK4 suppresses TNF-induced release of endothelial microparticles in HUVECs cells
Tumor necrosis factor-α (TNF) is a pro-inflammatory cytokine upregulated in many inflammatory diseases, and a potent inducer of endothelial cell-derived microparticle (EMP) formation. In this study, we identified the protein kinase PAK4 as a key regulator of the TNF-induced EMP release from human um...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377857/ https://www.ncbi.nlm.nih.gov/pubmed/32657762 http://dx.doi.org/10.18632/aging.103173 |
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author | Zhang, Shouqin Yin, Yingjie Li, Congye Zhao, Yi Wang, Qixing Zhang, Xiangyu |
author_facet | Zhang, Shouqin Yin, Yingjie Li, Congye Zhao, Yi Wang, Qixing Zhang, Xiangyu |
author_sort | Zhang, Shouqin |
collection | PubMed |
description | Tumor necrosis factor-α (TNF) is a pro-inflammatory cytokine upregulated in many inflammatory diseases, and a potent inducer of endothelial cell-derived microparticle (EMP) formation. In this study, we identified the protein kinase PAK4 as a key regulator of the TNF-induced EMP release from human umbilical vein endothelial cells (HUVECs). TNF induces dose- and time-dependent EMP release and downregulation of PAK4 and upstream cdc42 in HUVECs. PAK4 suppression or inhibition of its kinase activity increases TNF-induced EMP release and apoptosis in HUVECs, while PAK4 overexpression reduces EMP release and apoptosis in TNF-stimulated cells. Collectively, these data indicate that PAK4 suppresses TNF-induced EMP generation occurring during apoptosis, and suggest that modulation of PAK4 activity may represent a novel approach to suppress the TNF-induced EMP levels in pro-inflammatory disorders and other pathological conditions. |
format | Online Article Text |
id | pubmed-7377857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-73778572020-07-31 PAK4 suppresses TNF-induced release of endothelial microparticles in HUVECs cells Zhang, Shouqin Yin, Yingjie Li, Congye Zhao, Yi Wang, Qixing Zhang, Xiangyu Aging (Albany NY) Research Paper Tumor necrosis factor-α (TNF) is a pro-inflammatory cytokine upregulated in many inflammatory diseases, and a potent inducer of endothelial cell-derived microparticle (EMP) formation. In this study, we identified the protein kinase PAK4 as a key regulator of the TNF-induced EMP release from human umbilical vein endothelial cells (HUVECs). TNF induces dose- and time-dependent EMP release and downregulation of PAK4 and upstream cdc42 in HUVECs. PAK4 suppression or inhibition of its kinase activity increases TNF-induced EMP release and apoptosis in HUVECs, while PAK4 overexpression reduces EMP release and apoptosis in TNF-stimulated cells. Collectively, these data indicate that PAK4 suppresses TNF-induced EMP generation occurring during apoptosis, and suggest that modulation of PAK4 activity may represent a novel approach to suppress the TNF-induced EMP levels in pro-inflammatory disorders and other pathological conditions. Impact Journals 2020-07-12 /pmc/articles/PMC7377857/ /pubmed/32657762 http://dx.doi.org/10.18632/aging.103173 Text en Copyright © 2020 Zhang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Zhang, Shouqin Yin, Yingjie Li, Congye Zhao, Yi Wang, Qixing Zhang, Xiangyu PAK4 suppresses TNF-induced release of endothelial microparticles in HUVECs cells |
title | PAK4 suppresses TNF-induced release of endothelial microparticles in HUVECs cells |
title_full | PAK4 suppresses TNF-induced release of endothelial microparticles in HUVECs cells |
title_fullStr | PAK4 suppresses TNF-induced release of endothelial microparticles in HUVECs cells |
title_full_unstemmed | PAK4 suppresses TNF-induced release of endothelial microparticles in HUVECs cells |
title_short | PAK4 suppresses TNF-induced release of endothelial microparticles in HUVECs cells |
title_sort | pak4 suppresses tnf-induced release of endothelial microparticles in huvecs cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377857/ https://www.ncbi.nlm.nih.gov/pubmed/32657762 http://dx.doi.org/10.18632/aging.103173 |
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