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

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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.

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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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Authors and Affiliations

  1. Department of Cardiology, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China

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

  2. Department of Cardiology, Guizhou Provincial People’s Hospital, Guiyang, 550002, China

    Zong-Zhuang Li

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  1. Zong-Zhuang Li
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Correspondence to Qiu-Yan Dai.

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Zong-Zhuang Li and Zhen-Zhen Guo have contributed equally to this work.

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Li, ZZ., Guo, ZZ., Zhang, Z. et al. Nicotine-induced upregulation of VCAM-1, MMP-2, and MMP-9 through the α7-nAChR-JNK pathway in RAW264.7 and MOVAS cells. Mol Cell Biochem 399, 49–58 (2015). https://doi.org/10.1007/s11010-014-2231-z

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