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

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.