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...
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2015-01-01
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Series: | Mediators of Inflammation |
Online Access: | http://dx.doi.org/10.1155/2015/956082 |
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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 |
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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. |
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language | English |
publishDate | 2015-01-01 |
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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 |
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