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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Bibliographic Details
Published in:Mediators of inflammation 2016-01, Vol.2016 (2016), p.1-11
Main Authors: Dai, Qiu-Yan, Zhu, Ya-Juan, Zhang, Zhi, Liu, Li-Ping, Li, Zong-Zhuang, Cao, Qun-An, Guo, Zhen-Zhen, Chu, Guang
Format: Article
Language:English
Subjects:
Abdomen
Abdominal aneurysm
Aneurysms
Apolipoproteins
Cardiology
Chemokines
Coronary vessels
Cytokines
Drug dosages
Experiments
Extracellular matrix
Health aspects
Hospitals
Inflammation
Kinases
Laboratory animals
Macrophages
Medical research
Mortality
Nicotine
Physiological aspects
Proteins
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Summary: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.
ISSN:0962-9351
1466-1861
DOI:10.1155/2016/9142425