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Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Pro-inflammatory activities induced by CyPA-EMMPRIN interaction in monocytes
1Department of Cardiology, Ren Ji Hospital, Medical School of Shanghai Jiao Tong University, No. 1630 Dong Fang Road, 200127, Shanghai, People's Republic of China.
Cyclophilin A (CyPA) drives vascular inflammation in atherosclerosis by promoting monocyte migration and inflammatory cytokine release. Blocking EMMPRIN inhibits these CyPA-induced effects, revealing a key pathway for atherosclerosis therapy.
Area of Science:
- Cardiovascular Biology
- Immunology
- Molecular Medicine
Background:
- Excessive reactive oxygen species (ROS) drive vascular inflammation in atherosclerosis.
- Cyclophilin A (CyPA) is a key ROS-induced factor that enhances monocyte/macrophage inflammatory activity in atherosclerotic plaques.
- The precise interaction mechanisms between CyPA and monocytes/macrophages remain unclear.
Purpose of the Study:
- To elucidate the signaling pathway through which CyPA interacts with monocytes/macrophages.
- To investigate the role of extracellular matrix metalloproteinase inducer (EMMPRIN) in CyPA-mediated monocyte activation.
- To identify potential therapeutic targets for atherosclerosis.
Main Methods:
- Chemotaxis assays and ELISA tests were employed to assess monocyte migration and cytokine expression.
- Western blotting was used to analyze the activation of the NF-kappaB signaling pathway via ERK1/2.
- Monocytes were treated with CyPA, and the effects of blocking EMMPRIN were evaluated.
Main Results:
- CyPA significantly induced monocyte migration and the expression of mmp-9, IL-6, and TNF-alpha.
- CyPA activated the NF-kappaB pathway through ERK1/2.
- Blocking EMMPRIN in monocytes substantially inhibited CyPA-induced migration, NF-kappaB activation, and cytokine release.
- CyPA stimulation did not affect EMMPRIN expression in monocytes.
Conclusions:
- The CyPA-EMMPRIN interaction represents a critical pro-inflammatory signaling pathway in monocytes, particularly under ROS stimulation.
- This pathway is a potential therapeutic target for atherosclerosis.
- Understanding this interaction offers insights into managing vascular inflammation.
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