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...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/9142425 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841524644556832768 |
|---|---|
| author | Zhen-Zhen Guo Qun-An Cao Zong-Zhuang Li Li-Ping Liu Zhi Zhang Ya-Juan Zhu Guang Chu Qiu-Yan Dai |
| author_facet | Zhen-Zhen Guo Qun-An Cao Zong-Zhuang Li Li-Ping Liu Zhi Zhang Ya-Juan Zhu Guang Chu Qiu-Yan Dai |
| author_sort | Zhen-Zhen Guo |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-88dd039073bb45c299dd2efac655b112 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-88dd039073bb45c299dd2efac655b1122025-02-03T05:47:50ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/91424259142425SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage MigrationZhen-Zhen Guo0Qun-An Cao1Zong-Zhuang Li2Li-Ping Liu3Zhi Zhang4Ya-Juan Zhu5Guang Chu6Qiu-Yan Dai7Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Cardiology, Guizhou Provincial People’s Hospital, Guiyang 550002, ChinaDepartment of Cardiology, Yancheng First People’s Hospital, The Fourth Affiliated Hospital of Nantong Medical University, Jiangsu 224001, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, ChinaNicotine, 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.http://dx.doi.org/10.1155/2016/9142425 |
| spellingShingle | Zhen-Zhen Guo Qun-An Cao Zong-Zhuang Li Li-Ping Liu Zhi Zhang Ya-Juan Zhu Guang Chu Qiu-Yan Dai SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration Mediators of Inflammation |
| 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 |
| url | http://dx.doi.org/10.1155/2016/9142425 |
| work_keys_str_mv | AT zhenzhenguo sp600125attenuatesnicotinerelatedaorticaneurysmformationbyinhibitingmatrixmetalloproteinaseproductionandccchemokinemediatedmacrophagemigration AT qunancao sp600125attenuatesnicotinerelatedaorticaneurysmformationbyinhibitingmatrixmetalloproteinaseproductionandccchemokinemediatedmacrophagemigration AT zongzhuangli sp600125attenuatesnicotinerelatedaorticaneurysmformationbyinhibitingmatrixmetalloproteinaseproductionandccchemokinemediatedmacrophagemigration AT lipingliu sp600125attenuatesnicotinerelatedaorticaneurysmformationbyinhibitingmatrixmetalloproteinaseproductionandccchemokinemediatedmacrophagemigration AT zhizhang sp600125attenuatesnicotinerelatedaorticaneurysmformationbyinhibitingmatrixmetalloproteinaseproductionandccchemokinemediatedmacrophagemigration AT yajuanzhu sp600125attenuatesnicotinerelatedaorticaneurysmformationbyinhibitingmatrixmetalloproteinaseproductionandccchemokinemediatedmacrophagemigration AT guangchu sp600125attenuatesnicotinerelatedaorticaneurysmformationbyinhibitingmatrixmetalloproteinaseproductionandccchemokinemediatedmacrophagemigration AT qiuyandai sp600125attenuatesnicotinerelatedaorticaneurysmformationbyinhibitingmatrixmetalloproteinaseproductionandccchemokinemediatedmacrophagemigration |