Cargando…

DC-SIGN and Toll-like receptor 4 mediate oxidized low-density lipoprotein-induced inflammatory responses in macrophages

The regulation of inflammatory responses by innate immune receptors is recognized as a crucial step in the development of atherosclerosis, although the precise molecular mechanisms remain to be elucidated. This study focused on illustrating the roles of dendritic cell-specific intercellular adhesion...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Ke, Liu, Xinhe, Liu, Yan, Wang, Xinqiong, Cao, Lijuan, Zhang, Xiaojie, Xu, Chundi, Shen, Weifeng, Zhou, Tong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5468253/
https://www.ncbi.nlm.nih.gov/pubmed/28607410
http://dx.doi.org/10.1038/s41598-017-03740-7
_version_ 1783243395794206720
author Yang, Ke
Liu, Xinhe
Liu, Yan
Wang, Xinqiong
Cao, Lijuan
Zhang, Xiaojie
Xu, Chundi
Shen, Weifeng
Zhou, Tong
author_facet Yang, Ke
Liu, Xinhe
Liu, Yan
Wang, Xinqiong
Cao, Lijuan
Zhang, Xiaojie
Xu, Chundi
Shen, Weifeng
Zhou, Tong
author_sort Yang, Ke
collection PubMed
description The regulation of inflammatory responses by innate immune receptors is recognized as a crucial step in the development of atherosclerosis, although the precise molecular mechanisms remain to be elucidated. This study focused on illustrating the roles of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)- and Toll-like receptor 4 (TLR4)-regulated inflammatory responses in macrophages. We found that DC-SIGN expression levels were increased in macrophages of atherosclerotic plaques. Oxidized low-density lipoprotein (oxLDL) significantly enhanced DC-SIGN protein expression levels after a short-term exposure. Knockdown of DC-SIGN decreased expression and secretion of interleukin 1-β (IL1-β), monocyte chemo-attractant protein 1 (MCP-1), tumor necrosis factor-α (TNFα) and matrix metalloproteinase-9 (MMP-9). Immunofluorescence studies demonstrated that DC-SIGN and TLR4 co-localized in regions of the plaques. Moreover, DC-SIGN was co-expressed with TLR4 on the plasma membrane after oxLDL stimulation. The presence of an endogenous interaction and the results of the in vitro pull-down assays revealed that DC-SIGN binds directly with TLR4. We also present evidence that DC-SIGN mediates TLR4-regulated NFκB activation but not activation of p38 and JNK. Our results suggest an essential role of DC-SIGN/TLR4 signaling in macrophages in the pathogenesis of atherosclerosis.
format Online
Article
Text
id pubmed-5468253
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-54682532017-06-14 DC-SIGN and Toll-like receptor 4 mediate oxidized low-density lipoprotein-induced inflammatory responses in macrophages Yang, Ke Liu, Xinhe Liu, Yan Wang, Xinqiong Cao, Lijuan Zhang, Xiaojie Xu, Chundi Shen, Weifeng Zhou, Tong Sci Rep Article The regulation of inflammatory responses by innate immune receptors is recognized as a crucial step in the development of atherosclerosis, although the precise molecular mechanisms remain to be elucidated. This study focused on illustrating the roles of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)- and Toll-like receptor 4 (TLR4)-regulated inflammatory responses in macrophages. We found that DC-SIGN expression levels were increased in macrophages of atherosclerotic plaques. Oxidized low-density lipoprotein (oxLDL) significantly enhanced DC-SIGN protein expression levels after a short-term exposure. Knockdown of DC-SIGN decreased expression and secretion of interleukin 1-β (IL1-β), monocyte chemo-attractant protein 1 (MCP-1), tumor necrosis factor-α (TNFα) and matrix metalloproteinase-9 (MMP-9). Immunofluorescence studies demonstrated that DC-SIGN and TLR4 co-localized in regions of the plaques. Moreover, DC-SIGN was co-expressed with TLR4 on the plasma membrane after oxLDL stimulation. The presence of an endogenous interaction and the results of the in vitro pull-down assays revealed that DC-SIGN binds directly with TLR4. We also present evidence that DC-SIGN mediates TLR4-regulated NFκB activation but not activation of p38 and JNK. Our results suggest an essential role of DC-SIGN/TLR4 signaling in macrophages in the pathogenesis of atherosclerosis. Nature Publishing Group UK 2017-06-12 /pmc/articles/PMC5468253/ /pubmed/28607410 http://dx.doi.org/10.1038/s41598-017-03740-7 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yang, Ke
Liu, Xinhe
Liu, Yan
Wang, Xinqiong
Cao, Lijuan
Zhang, Xiaojie
Xu, Chundi
Shen, Weifeng
Zhou, Tong
DC-SIGN and Toll-like receptor 4 mediate oxidized low-density lipoprotein-induced inflammatory responses in macrophages
title DC-SIGN and Toll-like receptor 4 mediate oxidized low-density lipoprotein-induced inflammatory responses in macrophages
title_full DC-SIGN and Toll-like receptor 4 mediate oxidized low-density lipoprotein-induced inflammatory responses in macrophages
title_fullStr DC-SIGN and Toll-like receptor 4 mediate oxidized low-density lipoprotein-induced inflammatory responses in macrophages
title_full_unstemmed DC-SIGN and Toll-like receptor 4 mediate oxidized low-density lipoprotein-induced inflammatory responses in macrophages
title_short DC-SIGN and Toll-like receptor 4 mediate oxidized low-density lipoprotein-induced inflammatory responses in macrophages
title_sort dc-sign and toll-like receptor 4 mediate oxidized low-density lipoprotein-induced inflammatory responses in macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5468253/
https://www.ncbi.nlm.nih.gov/pubmed/28607410
http://dx.doi.org/10.1038/s41598-017-03740-7
work_keys_str_mv AT yangke dcsignandtolllikereceptor4mediateoxidizedlowdensitylipoproteininducedinflammatoryresponsesinmacrophages
AT liuxinhe dcsignandtolllikereceptor4mediateoxidizedlowdensitylipoproteininducedinflammatoryresponsesinmacrophages
AT liuyan dcsignandtolllikereceptor4mediateoxidizedlowdensitylipoproteininducedinflammatoryresponsesinmacrophages
AT wangxinqiong dcsignandtolllikereceptor4mediateoxidizedlowdensitylipoproteininducedinflammatoryresponsesinmacrophages
AT caolijuan dcsignandtolllikereceptor4mediateoxidizedlowdensitylipoproteininducedinflammatoryresponsesinmacrophages
AT zhangxiaojie dcsignandtolllikereceptor4mediateoxidizedlowdensitylipoproteininducedinflammatoryresponsesinmacrophages
AT xuchundi dcsignandtolllikereceptor4mediateoxidizedlowdensitylipoproteininducedinflammatoryresponsesinmacrophages
AT shenweifeng dcsignandtolllikereceptor4mediateoxidizedlowdensitylipoproteininducedinflammatoryresponsesinmacrophages
AT zhoutong dcsignandtolllikereceptor4mediateoxidizedlowdensitylipoproteininducedinflammatoryresponsesinmacrophages