Pro-inflammatory activities induced by CyPA-EMMPRIN interaction in monocytes |
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Authors: | Yuan Wei Ge Heng He Ben |
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Institution: | Department of Cardiology, Ren Ji Hospital, Medical School of Shanghai Jiao Tong University, No. 1630 Dong Fang Road, 200127, Shanghai, People's Republic of China. |
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Abstract: | Excessive reactive oxygen species (ROS) is a critical driver of vascular inflammation in atherosclerosis. Cyclophilin A (CyPA) is the main ROS-induced factor that enhances the inflammatory activity of monocytes/macrophages in atherosclerotic plaque. However, the means by which CyPA interacts with monocytes/macrophages is unclear. Through Chemotaxis assay and ELISA test, we found CyPA strongly induced migration of monocytes and the expression of mmp-9, IL-6 and TNF-alpha. By Western blot, it demonstrated that CyPA activated NF-kappaB by ERK1/2 pathway. When blocking extracellular matrix metalloproteinase inducer (EMMPRIN) in monocytes, most of the CyPA effects including chemoattractant migration, activation of MAPK/NF-kappaB and cytokines releasing were significantly inhibited. Finally, CyPA simulation had no effect on EMMPRIN expression in monocytes. The current study shows that CyPA-EMMPRIN interaction is one of the key pro-inflammatory signaling pathways in monocytes, perhaps especially in response to ROS stimulation. This could be a potential target for atherosclerosis therapy. |
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