Paeonol enhances macrophage phagocytic function by modulating lipid metabolism through the P53-TREM2 axis

Abstract

Abstract Background The emerging concept of immunometabolism highlights the interplay between lipid metabolism and phagocytosis in macrophages. Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) has been identified as an important modulator of both lipid metabolism and phagocytic function in macrophages. This study aims to investigate the roles of P53 and TREM2 in regulating macrophage lipid metabolism and phagocytosis and to evaluate the potential therapeutic effects of Paeonol on these processes.Methods CRISPR-Cas9 was utilized to generate P53 and TREM2 knockout RAW264.7 cell lines. The dual-luciferase reporter gene assay was performed to assess the interaction between P53 and the TREM2 promoter. A series of functional assays were conducted to evaluate the impact of P53 and TREM2 on macrophage lipid metabolism and phagocytic function. The effects of Paeonol on these processes were also examined.Results Our findings revealed that P53 acts as a transcription factor that upregulates the expression of TREM2, promoting macrophage lipid metabolism, metabolic activity, and phagocytic capacity. Paeonol treatment significantly enhanced the phagocytic function of macrophages. Additionally, the interaction between P53 and the TREM2 promoter was confirmed through dual-luciferase reporter gene assays.Conclusions This study provides novel insights into the roles of P53 and TREM2 in regulating macrophage lipid metabolism and phagocytic function. Furthermore, our findings suggest that Paeonol could be a promising therapeutic agent for modulating macrophage function in various diseases. Further research is warranted to explore the potential applications of Paeonol and to elucidate the molecular mechanisms underlying the observed effects.