TIPE2 suppresses atherosclerosis by exerting a protective effect on macrophages via the inhibition of the Akt signaling pathway

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.