PMID:
Int J Clin Exp Pathol. 2019 ;12(10):3791-3798. Epub 2019 Oct 1. PMID: 31933767
Abstract Title:
Tanshinone IIA reduces oxidized low-density lipoprotein-induced inflammatory responses by downregulating microRNA-33 in THP-1 macrophages.
Abstract:
Atherosclerosis is a leading cause of cardiovascular diseases. Oxidized low-density lipoprotein (ox-LDL) is commonly used to construct atherosclerosis cell models. Macrophages-secreted pro-inflammatory factors play vital roles in the development of atherosclerosis. Tanshinone IIA (Tan) is an effective therapeutic agent for atherosclerotic cardiovascular diseases. However, the molecular mechanisms by which Tan protects against atherogenesis have not been thoroughly elucidated. In the present study, we aimed to search for microRNA targets of Tan in ox-LDL-stimulated macrophages. Interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) levels were determined by matching ELISA commercial kits. RT-qPCR assay was conducted to measure microRNA-33 (miR-33) expression. We found that ox-LDL induced the secretion of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and the expressionof microRNA-33 (miR-33) in THP-1 macrophages. Tan inhibited pro-inflammatory cytokine secretion and miR-33 expression in ox-LDL-stimulated THP-1 macrophages. Also, the depletion of miR-33 suppressed pro-inflammatory cytokine secretion in ox-LDL-stimulated THP-1 macrophages. Moreover, miR-33 upregulation abrogated the inhibitory effect of Tan on pro-inflammatory cytokine secretion in ox-LDL-stimulated THP-1 macrophages. In conclusion, Tan inhibited ox-LDL-induced pro-inflammatory cytokine secretion by downregulating miR-33 in THP-1 macrophages, hinting that Tan might exert its atheroprotectiveeffects by targeting miR-33 and reducing pro-inflammatory responses.
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