SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration
| Autor: | Zong-Zhuang Li, Zhen-Zhen Guo, Guang Chu, Ya-Juan Zhu, Qiuyan Dai, Zhi Zhang, Qunan Cao, Liping Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Chemokine Vascular smooth muscle Article Subject Immunology 030204 cardiovascular system & hematology Pharmacology Matrix metalloproteinase Nicotine 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine lcsh:Pathology Macrophage biology Chemistry Kinase Cell Biology Angiotensin II 030104 developmental biology biology.protein cardiovascular system medicine.drug Research Article lcsh:RB1-214 |
| Zdroj: | Mediators of Inflammation, Vol 2016 (2016) Mediators of Inflammation |
| ISSN: | 0962-9351 |
| DOI: | 10.1155/2016/9142425 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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