Knock-down MALAT1 reduces ox-LDL- induced-inflammation and cell damage of macrophages

Objective To explore the role and potential mechanism of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in inflammatory response and cell damage of macrophages induced by oxidized low density lipoprotein (ox-LDL). Methods THP-1 cells were induced to differentiate into macrophages by phorbol ester(PMA). Macrophages were co-cultured with ox-LDL to construct a cell injury model. Lipid accumulation was observed by Oil Red O staining microscopy. MALAT1 was knocked down by transfection of shRNA. The experimental group included control group, ox-LDL group, ox-LDL+shNC group and ox-LDL+shMALAT1 group. Total cholesterol and triglyceride in cells were measured. Apoptosis was detected by flow cytometry. The level of IL-6, TNFα and MCP-1 were detected by ELISA. The expression of NLRP3, RIPK1, caspase-8, p65 and SR-A was detected by RT-qPCR and Western blot. Results Compared with the control group, the cell lipid accumulation, total cholesterol and triglyceride contents, cell apoptosis, IL-6, TNFα and MCP-1 levels and the expression of NLRP3, RIPK1, caspase-8, p-p65 and SR-A increased significantly in ox-LDL group(P＜0.05). Compared with ox-LDL group, ox-LDL+shMALAT1 group the contents of total cholesterol and triglyceride, apoptosis, IL-6, TNFα and MCP-1, and the expression of NLRP3, RIPK1, caspase-8, p-p65 and SR-A all significantly decreased(P＜0.05). Conclusions MALAT1 may play an important role in ox-LDL-induced cell injury by regulating NLRP3 inflammatory corpuscles and related signal pathways. Knockdown of MALAT1 can significantly reduce the inflammatory reaction and cell damage induced by ox-LDL, which provides a potential target for the treatment of atherosclerosis.