Molecular and Cellular Biochemistry

, Volume 399, Issue 1–2, pp 49–58 | Cite as

Nicotine-induced upregulation of VCAM-1, MMP-2, and MMP-9 through the α7-nAChR-JNK pathway in RAW264.7 and MOVAS cells

  • Zong-Zhuang Li
  • Zhen-Zhen Guo
  • Zhi Zhang
  • Qun-An Cao
  • Ya-Juan Zhu
  • Hua-Li Yao
  • Li-Li Wu
  • Qiu-Yan Dai
Article

Abstract

The ability of nicotine to induce aortic aneurysms has been shown in animal models; however, its underlying mechanisms remain elusive. In the present experiment, both the RAW264.7 and MOVAS cell lines were employed to examine the nicotine-induced modulation of VCAM-1, MMP-2, and MMP-9 expressions in macrophages and vascular smooth muscle cells. Our results showed that nicotine concentrations of both 0.5 and 5 ng/ml induced VCAM-1, MMP-2, and MMP-9 upregulation, while a concentration of 50 ng/ml had a slight inhibitory effect and a concentration of 500 ng/ml showed a significant inhibitory effect. When cells were pretreated with either SP600125 (JNK inhibitor) or PNU-282987 (α7-nAChR agonist) prior to nicotine exposure, the nicotine-induced upregulation of VCAM-1, MMP-2, MMP-9, and p-JNK was suppressed, with a joint treatment producing a more significant inhibitory effect. Moreover, PNU-282987 had a comparable inhibitory effect on VCAM-1, MMP-2, and MMP-9 expressions and JNK activation via phosphorylation as did SP600125. In conclusion, nicotine-induced VCAM-1, MMP-2, and MMP-9 expressions occur in a dose-dependent fashion in both of the cell lines tested. Furthermore, the nicotine exposure equivalent to plasma levels found in regular smokers can augment VCAM-1, MMP-2, and MMP-9 expressions through the α7-nAChR-JNK pathway.

Keywords

Nicotine JNK Nicotinic acetylcholine receptors Vascular cell adhesion molecular Matrix metalloproteinase 

Notes

Acknowledgments

This work was supported by grants from Natural Science Foundation of China (NSFC; no. 81370415), the Shanghai Science Committee, Shanghai, China (no. 09JC1412300) and Guizhou Provincial Science and Technology Fund Committee, Guiyang, China. (no. 2014GZ21763)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Zong-Zhuang Li
    • 1
    • 2
  • Zhen-Zhen Guo
    • 1
  • Zhi Zhang
    • 1
  • Qun-An Cao
    • 1
  • Ya-Juan Zhu
    • 1
  • Hua-Li Yao
    • 1
  • Li-Li Wu
    • 1
  • Qiu-Yan Dai
    • 1
  1. 1.Department of Cardiology, Shanghai First People’s Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
  2. 2.Department of CardiologyGuizhou Provincial People’s HospitalGuiyangChina

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