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SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration

Nicotine, a major chemical component of cigarettes, plays a pivotal role in the development of abdominal aortic aneurysm (AAA). c-Jun N-terminal kinase (JNK) has been demonstrated to participate in elastase-induced AAA. This study aimed to elucidate whether the JNK inhibitor SP600125 can attenuate n...

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Autores principales: Guo, Zhen-Zhen, Cao, Qun-An, Li, Zong-Zhuang, Liu, Li-Ping, Zhang, Zhi, Zhu, Ya-Juan, Chu, Guang, Dai, Qiu-Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023844/
https://www.ncbi.nlm.nih.gov/pubmed/27688602
http://dx.doi.org/10.1155/2016/9142425
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author Guo, Zhen-Zhen
Cao, Qun-An
Li, Zong-Zhuang
Liu, Li-Ping
Zhang, Zhi
Zhu, Ya-Juan
Chu, Guang
Dai, Qiu-Yan
author_facet Guo, Zhen-Zhen
Cao, Qun-An
Li, Zong-Zhuang
Liu, Li-Ping
Zhang, Zhi
Zhu, Ya-Juan
Chu, Guang
Dai, Qiu-Yan
author_sort Guo, Zhen-Zhen
collection PubMed
description Nicotine, a major chemical component of cigarettes, plays a pivotal role in the development of abdominal aortic aneurysm (AAA). c-Jun N-terminal kinase (JNK) has been demonstrated to participate in elastase-induced AAA. This study aimed to elucidate whether the JNK inhibitor SP600125 can attenuate nicotine plus angiotensin II- (AngII-) induced AAA formation and to assess the underlying molecular mechanisms. SP600125 significantly attenuated nicotine plus AngII-induced AAA formation. The expression of matrix metalloproteinase- (MMP-) 2, MMP-9, monocyte chemoattractant protein- (MCP-) 1, and regulated-on-activation, normal T-cells expressed and secreted (RANTES) was significantly upregulated in aortic aneurysm lesions but inhibited by SP600125. In vitro, nicotine induced the expression of MCP-1 and RANTES in both RAW264.7 (mouse macrophage) and MOVAS (mouse vascular smooth muscle) cells in a dose-dependent manner; expression was upregulated by 0.5 ng/mL nicotine but strongly downregulated by 500 ng/mL nicotine. SP600125 attenuated the upregulation of MCP-1 and RANTES expression and subsequent macrophage migration. In conclusion, SP600125 attenuates nicotine plus AngII-induced AAA formation likely by inhibiting MMP-2, MMP-9, MCP-1, and RANTES. The expression of chemokines in MOVAS cells induced by nicotine has an effect on RAW264.7 migration, which is likely to contribute to the development of nicotine-related AAA.
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spelling pubmed-50238442016-09-29 SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration Guo, Zhen-Zhen Cao, Qun-An Li, Zong-Zhuang Liu, Li-Ping Zhang, Zhi Zhu, Ya-Juan Chu, Guang Dai, Qiu-Yan Mediators Inflamm Research Article Nicotine, a major chemical component of cigarettes, plays a pivotal role in the development of abdominal aortic aneurysm (AAA). c-Jun N-terminal kinase (JNK) has been demonstrated to participate in elastase-induced AAA. This study aimed to elucidate whether the JNK inhibitor SP600125 can attenuate nicotine plus angiotensin II- (AngII-) induced AAA formation and to assess the underlying molecular mechanisms. SP600125 significantly attenuated nicotine plus AngII-induced AAA formation. The expression of matrix metalloproteinase- (MMP-) 2, MMP-9, monocyte chemoattractant protein- (MCP-) 1, and regulated-on-activation, normal T-cells expressed and secreted (RANTES) was significantly upregulated in aortic aneurysm lesions but inhibited by SP600125. In vitro, nicotine induced the expression of MCP-1 and RANTES in both RAW264.7 (mouse macrophage) and MOVAS (mouse vascular smooth muscle) cells in a dose-dependent manner; expression was upregulated by 0.5 ng/mL nicotine but strongly downregulated by 500 ng/mL nicotine. SP600125 attenuated the upregulation of MCP-1 and RANTES expression and subsequent macrophage migration. In conclusion, SP600125 attenuates nicotine plus AngII-induced AAA formation likely by inhibiting MMP-2, MMP-9, MCP-1, and RANTES. The expression of chemokines in MOVAS cells induced by nicotine has an effect on RAW264.7 migration, which is likely to contribute to the development of nicotine-related AAA. Hindawi Publishing Corporation 2016 2016-09-01 /pmc/articles/PMC5023844/ /pubmed/27688602 http://dx.doi.org/10.1155/2016/9142425 Text en Copyright © 2016 Zhen-Zhen Guo et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Guo, Zhen-Zhen
Cao, Qun-An
Li, Zong-Zhuang
Liu, Li-Ping
Zhang, Zhi
Zhu, Ya-Juan
Chu, Guang
Dai, Qiu-Yan
SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration
title SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration
title_full SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration
title_fullStr SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration
title_full_unstemmed SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration
title_short SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration
title_sort sp600125 attenuates nicotine-related aortic aneurysm formation by inhibiting matrix metalloproteinase production and cc chemokine-mediated macrophage migration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023844/
https://www.ncbi.nlm.nih.gov/pubmed/27688602
http://dx.doi.org/10.1155/2016/9142425
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