Abstract
Macrophage apoptosis and inflammation serve pivotal roles in the occurrence of atherosclerosis. However, the detailed underlying mechanism of macrophage action during atherosclerosis is poorly understood. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a well-known negative regulator of the immune response. The current study assessed the association between TIPE2 and apoptosis-associated molecules in macrophages during atherosclerosis, as well as the role of TIPE2 in macrophage inflammation. RAW264.7 macrophages were subsequently transfected with a TIPE2 expression plasmid. Following oxidized low-density lipoprotein (oxLDL) induction (100 µg/m1) for 48 h, macrophage apoptosis was assessed via Annexin V/propidium iodide dual staining. The apoptosis-associated factors and Akt signaling pathway-associated factors were also evaluated via western blot analysis. The expression of inflammatory factors was determined via a reverse transcription-quantitative polymerase chain reaction assay and western blotting. Furthermore, a transwell assay was performed to test cell invasion ability. NF-κB phosphorylation and nuclear translocation were also assessed via western blotting. The results demonstrated that TIPE2 overexpression may promote oxLDL-induced RAW264.7 macrophage apoptosis by inhibiting the protein kinase B (Akt) signaling pathway. Furthermore, it was demonstrated that TIPE2 significantly reduced oxLDL-induced tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 expression (MCP-1), and increased IL-10 expression by suppressing NF-κB phosphorylation and nuclear translocation in RAW264.7 macrophages. These results indicated that TIPE2 serves a protective role in oxLDL-induced RAW264.7 macrophages, and its mechanism may partly be exerted via the inhibition of the PI3K/Akt signaling pathway and the reduction of the macrophage inflammatory response achieved via the suppression of NF-κB signal activation.