Nicotine-induced upregulation of VCAM-1, MMP-2, and MMP-9 through the α7-nAChR-JNK pathway in RAW264.7 and MOVAS cells
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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DOI：
10.1007/s11010-014-2231-z
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发表时间：
2015-01-01
影响因子：
4.3
通讯作者：
Dai, Qiu-Yan
中科院分区：
文献类型：
--
作者：
Li, Zong-Zhuang;Guo, Zhen-Zhen;Dai, Qiu-Yan
尼古丁诱导主动脉瘤的能力已在动物模型中得到证实;然而，其潜在机制仍然难以捉摸。在本实验中，使用RAW264.7和MOVAS细胞系来检测尼古丁诱导的巨噬细胞和血管平滑肌细胞中VCAM-1、MMP-2和MMP-9表达的调节。我们的结果表明，尼古丁浓度为0.5和5 ng/ml诱导VCAM-1，MMP-2和MMP-9上调，而浓度为50 ng/ml有轻微的抑制作用，浓度为500 ng/ml显示出显着的抑制作用。当细胞在尼古丁暴露之前用SP 600125（JNK抑制剂）或PNU-282987（α 7-nAChR激动剂）预处理时，尼古丁诱导的VCAM-1、MMP-2、MMP-9和p-JNK的上调被抑制，联合处理产生更显著的抑制作用。此外，PNU-282987通过磷酸化对VCAM-1、MMP-2和MMP-9表达和JNK活化具有与SP 600125相当的抑制作用。总之，尼古丁诱导的VCAM-1，MMP-2和MMP-9的表达发生在两个测试的细胞系中的剂量依赖性的方式。此外，尼古丁暴露等同于常规吸烟者的血浆水平，可通过α 7-nAChR-JNK途径增加VCAM-1、MMP-2和MMP-9的表达。
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 (alpha 7-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 alpha 7-nAChR-JNK pathway.