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Tim-3 inhibits low-density lipoprotein-induced atherogenic responses in human umbilical vein endothelial cells
Endothelial injury and dysfunction followed by endothelial activation and inflammatory cell recruitment are factors contributing to the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) promotes inflammation during atherogenesis and lipid deposition in the arte...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617401/ https://www.ncbi.nlm.nih.gov/pubmed/28977841 http://dx.doi.org/10.18632/oncotarget.17720 |
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author | Qiu, Ming-Ke Wang, Song-Cun Tang, Yong Pan, Chang Wang, Yang Wang, Shu-Qing Quan, Zhi-Wei Ou, Jing-Min |
author_facet | Qiu, Ming-Ke Wang, Song-Cun Tang, Yong Pan, Chang Wang, Yang Wang, Shu-Qing Quan, Zhi-Wei Ou, Jing-Min |
author_sort | Qiu, Ming-Ke |
collection | PubMed |
description | Endothelial injury and dysfunction followed by endothelial activation and inflammatory cell recruitment are factors contributing to the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) promotes inflammation during atherogenesis and lipid deposition in the arterial wall. We observed that stimulation of human umbilical vein endothelial cells (HUVECs) with ox-LDL activated pro-inflammatory cytokine production and apoptosis, inhibited cell migration, and upregulated T-cell immunoglobulin and mucin domain 3 (Tim-3) expression. Tim-3, in turn, protected HUVECs from ox-LDL-induced apoptosis via the JNK pathway and reversed the inhibition of migration. Tim-3 also inhibited ox-LDL-induced inflammatory cytokine production by suppressing NF-κB activation. In addition, Tim-3 increased production of type 2 T helper cells (Th2) and regulatory T cell (Treg)-associated cytokines. Blocking Tim-3 reversed its effects on the inflammatory response to ox-LDL. Thus, Tim-3 signaling may be a “self-control” mechanism in ox-LDL-triggered inflammation in HUVECs. These results identify Tim-3 as a factor in HUVEC activity and suggest its potential in the treatment of atherosclerosis. |
format | Online Article Text |
id | pubmed-5617401 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56174012017-10-03 Tim-3 inhibits low-density lipoprotein-induced atherogenic responses in human umbilical vein endothelial cells Qiu, Ming-Ke Wang, Song-Cun Tang, Yong Pan, Chang Wang, Yang Wang, Shu-Qing Quan, Zhi-Wei Ou, Jing-Min Oncotarget Research Paper Endothelial injury and dysfunction followed by endothelial activation and inflammatory cell recruitment are factors contributing to the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) promotes inflammation during atherogenesis and lipid deposition in the arterial wall. We observed that stimulation of human umbilical vein endothelial cells (HUVECs) with ox-LDL activated pro-inflammatory cytokine production and apoptosis, inhibited cell migration, and upregulated T-cell immunoglobulin and mucin domain 3 (Tim-3) expression. Tim-3, in turn, protected HUVECs from ox-LDL-induced apoptosis via the JNK pathway and reversed the inhibition of migration. Tim-3 also inhibited ox-LDL-induced inflammatory cytokine production by suppressing NF-κB activation. In addition, Tim-3 increased production of type 2 T helper cells (Th2) and regulatory T cell (Treg)-associated cytokines. Blocking Tim-3 reversed its effects on the inflammatory response to ox-LDL. Thus, Tim-3 signaling may be a “self-control” mechanism in ox-LDL-triggered inflammation in HUVECs. These results identify Tim-3 as a factor in HUVEC activity and suggest its potential in the treatment of atherosclerosis. Impact Journals LLC 2017-05-09 /pmc/articles/PMC5617401/ /pubmed/28977841 http://dx.doi.org/10.18632/oncotarget.17720 Text en Copyright: © 2017 Qiu 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 (http://creativecommons.org/licenses/by/3.0/) 3.0 (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 Qiu, Ming-Ke Wang, Song-Cun Tang, Yong Pan, Chang Wang, Yang Wang, Shu-Qing Quan, Zhi-Wei Ou, Jing-Min Tim-3 inhibits low-density lipoprotein-induced atherogenic responses in human umbilical vein endothelial cells |
title | Tim-3 inhibits low-density lipoprotein-induced atherogenic responses in human umbilical vein endothelial cells |
title_full | Tim-3 inhibits low-density lipoprotein-induced atherogenic responses in human umbilical vein endothelial cells |
title_fullStr | Tim-3 inhibits low-density lipoprotein-induced atherogenic responses in human umbilical vein endothelial cells |
title_full_unstemmed | Tim-3 inhibits low-density lipoprotein-induced atherogenic responses in human umbilical vein endothelial cells |
title_short | Tim-3 inhibits low-density lipoprotein-induced atherogenic responses in human umbilical vein endothelial cells |
title_sort | tim-3 inhibits low-density lipoprotein-induced atherogenic responses in human umbilical vein endothelial cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617401/ https://www.ncbi.nlm.nih.gov/pubmed/28977841 http://dx.doi.org/10.18632/oncotarget.17720 |
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