Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting

Inflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS). Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1β, IL-6, T...

Full description

Saved in:
Bibliographic Details
Main Authors: Rongrong Zhang, Fan Jiang, Cindy Si Chen, Tianzhu Wang, Jinzhou Feng, Tao Tao, Xinyue Qin
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2015/956082
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832552920560697344
author Rongrong Zhang
Fan Jiang
Cindy Si Chen
Tianzhu Wang
Jinzhou Feng
Tao Tao
Xinyue Qin
author_facet Rongrong Zhang
Fan Jiang
Cindy Si Chen
Tianzhu Wang
Jinzhou Feng
Tao Tao
Xinyue Qin
author_sort Rongrong Zhang
collection DOAJ
description Inflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS). Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1β, IL-6, TGF-β, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months. Second, we established a new in vitro model, where THP-1 monocytes were treated with the supernatants of human umbilical vein endothelial cells (HUVECs) that were scratched by pipette tips, which mimics monocytes activated by mechanical injury of stenting. The treatment enhanced THP-1 cell adhesion, migration and invasion ability, and the phosphorylation of ERK1/2 and Elk-1 and MMP-9 expression were significantly increased. THP-1 cells pretreated with PD98095 (ERK1/2 inhibitor) attenuated the phosphorylation of ERK1/2 and Elk-1 and upregulation of MMP-9, while pretreatment with telmisartan merely decreased the phosphorylation of Elk-1 and MMP-9 expression. These results suggested that IL-1β, IL-6, TGF-β, and MMP-9 participate in the pathophysiological process after CAS. Our new in vitro model mimics monocytes activated by stenting. MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.
format Article
id doaj-art-683db1d0c35940419e74b137ecffac50
institution Kabale University
issn 0962-9351
1466-1861
language English
publishDate 2015-01-01
publisher Wiley
record_format Article
series Mediators of Inflammation
spelling doaj-art-683db1d0c35940419e74b137ecffac502025-02-03T05:57:32ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/956082956082Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by StentingRongrong Zhang0Fan Jiang1Cindy Si Chen2Tianzhu Wang3Jinzhou Feng4Tao Tao5Xinyue Qin6Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, The Fifth People’s Hospital of Chongqing, Chongqing 400062, ChinaDepartment of Medicine, Drexel University College of Medicine, Philadelphia, PA 19129, USADepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaInflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS). Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1β, IL-6, TGF-β, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months. Second, we established a new in vitro model, where THP-1 monocytes were treated with the supernatants of human umbilical vein endothelial cells (HUVECs) that were scratched by pipette tips, which mimics monocytes activated by mechanical injury of stenting. The treatment enhanced THP-1 cell adhesion, migration and invasion ability, and the phosphorylation of ERK1/2 and Elk-1 and MMP-9 expression were significantly increased. THP-1 cells pretreated with PD98095 (ERK1/2 inhibitor) attenuated the phosphorylation of ERK1/2 and Elk-1 and upregulation of MMP-9, while pretreatment with telmisartan merely decreased the phosphorylation of Elk-1 and MMP-9 expression. These results suggested that IL-1β, IL-6, TGF-β, and MMP-9 participate in the pathophysiological process after CAS. Our new in vitro model mimics monocytes activated by stenting. MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.http://dx.doi.org/10.1155/2015/956082
spellingShingle Rongrong Zhang
Fan Jiang
Cindy Si Chen
Tianzhu Wang
Jinzhou Feng
Tao Tao
Xinyue Qin
Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting
Mediators of Inflammation
title Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting
title_full Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting
title_fullStr Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting
title_full_unstemmed Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting
title_short Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting
title_sort serum levels of il 1β il 6 tgf β and mmp 9 in patients undergoing carotid artery stenting and regulation of mmp 9 in a new in vitro model of thp 1 cells activated by stenting
url http://dx.doi.org/10.1155/2015/956082
work_keys_str_mv AT rongrongzhang serumlevelsofil1bil6tgfbandmmp9inpatientsundergoingcarotidarterystentingandregulationofmmp9inanewinvitromodelofthp1cellsactivatedbystenting
AT fanjiang serumlevelsofil1bil6tgfbandmmp9inpatientsundergoingcarotidarterystentingandregulationofmmp9inanewinvitromodelofthp1cellsactivatedbystenting
AT cindysichen serumlevelsofil1bil6tgfbandmmp9inpatientsundergoingcarotidarterystentingandregulationofmmp9inanewinvitromodelofthp1cellsactivatedbystenting
AT tianzhuwang serumlevelsofil1bil6tgfbandmmp9inpatientsundergoingcarotidarterystentingandregulationofmmp9inanewinvitromodelofthp1cellsactivatedbystenting
AT jinzhoufeng serumlevelsofil1bil6tgfbandmmp9inpatientsundergoingcarotidarterystentingandregulationofmmp9inanewinvitromodelofthp1cellsactivatedbystenting
AT taotao serumlevelsofil1bil6tgfbandmmp9inpatientsundergoingcarotidarterystentingandregulationofmmp9inanewinvitromodelofthp1cellsactivatedbystenting
AT xinyueqin serumlevelsofil1bil6tgfbandmmp9inpatientsundergoingcarotidarterystentingandregulationofmmp9inanewinvitromodelofthp1cellsactivatedbystenting