著者

Xiang Yin Linli Zhou Fei Han Jie Han Yuanyuan Zhang Zewei Sun Wenting Zhao Zhen Wang Liangrong Zheng

出版者

一般社団法人 日本動脈硬化学会

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.24, no.1, pp.55-67, 2017-01-01 (Released:2017-01-01)

参考文献数

30

被引用文献数

9

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Aim: Atherosclerosis is a chronic inflammatory disease, which leads to thrombosis and acute coronary syndrome. Matrix metalloproteinase-9 (MMP-9) is involved in the stability of the extracellular matrix (ECM) and atherosclerosis plaque. Until now, it is established that lipopolysaccharide (LPS) and norepinephrine (NE) are associated with the pathological process of atherosclerosis. However, the combined effect of LPS and NE on MMP-9 is unclear. We investigated the combined effect of LPS and NE on MMP-9 expression in human monocytes and the mechanism involved in the process.Methods: THP-1 cells were cultured and treated with LPS and/or NE. MMP-9 and TIMP-1 gene and protein expression were detected by real time PCR and ELISA, respectively. MMP-9 activity was detected by gelatin zymography. Adrenoceptor antagonists and MAPKs inhibitors were used to clarify the mechanism. Pathway-related proteins were detected by Western blot.Results: We found that NE enhances LPS-induced MMP-9 and TIMP-1 expression as well as MMP-9 activity in THP-1 cells. This effect is reversed by the beta (β)-adrenoceptor antagonist propranolol, extracellular signal-regulated kinases (ERK) inhibitor U0126, and c-Jun N-terminal kinase (JNK) inhibitor SP600125. NE enhances LPS-induced ERK/JNK phosphorylation. NE up-regulates LPS-induced c-Fos expression, which is counteracted by propranolol, U0126, and SP600125. Furthermore, c-Fos silence reverses the effect of NE on MMP-9 activity.Conclusions: Our results suggest that NE enhances LPS-induced MMP-9 expression through β-adrenergic receptor and downstream ERK/JNK-c-Fos pathway. This study may help us to understand the combined effect and mechanism of NE/LPS on MMP-9 expression.