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

Introduction: 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 essential modulator of both lipid metabolism and phagocytic function in macroph...

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Autores principales: Miao, Jifei, Liu, Xiaoming, Liao, Yuanpin, Li, Yiwen, Kuang, Yingyan, Zheng, Juanxia, Li, Zigang, Lan, Jiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338837/
https://www.ncbi.nlm.nih.gov/pubmed/37456739
http://dx.doi.org/10.3389/fphar.2023.1214756
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author Miao, Jifei
Liu, Xiaoming
Liao, Yuanpin
Li, Yiwen
Kuang, Yingyan
Zheng, Juanxia
Li, Zigang
Lan, Jiao
author_facet Miao, Jifei
Liu, Xiaoming
Liao, Yuanpin
Li, Yiwen
Kuang, Yingyan
Zheng, Juanxia
Li, Zigang
Lan, Jiao
author_sort Miao, Jifei
collection PubMed
description Introduction: 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 essential 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 paeonol induces the accumulation of P53 in the nucleus. P53 acts as a transcription factor that upregulates the expression of TREM2, promoting macrophage lipid metabolism, metabolic activity, and phagocytic capacity. Additionally, dual-luciferase reporter gene assays confirmed the interaction between P53 and the TREM2 promoter. Discussion: This study provides novel insights into the roles of P53 and TREM2 in regulating macrophage lipid metabolism and phagocytic function. Further research is warranted to explore the potential applications of Paeonol and to elucidate the molecular mechanisms underlying the observed effects.
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spelling pubmed-103388372023-07-14 Paeonol enhances macrophage phagocytic function by modulating lipid metabolism through the P53-TREM2 axis Miao, Jifei Liu, Xiaoming Liao, Yuanpin Li, Yiwen Kuang, Yingyan Zheng, Juanxia Li, Zigang Lan, Jiao Front Pharmacol Pharmacology Introduction: 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 essential 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 paeonol induces the accumulation of P53 in the nucleus. P53 acts as a transcription factor that upregulates the expression of TREM2, promoting macrophage lipid metabolism, metabolic activity, and phagocytic capacity. Additionally, dual-luciferase reporter gene assays confirmed the interaction between P53 and the TREM2 promoter. Discussion: This study provides novel insights into the roles of P53 and TREM2 in regulating macrophage lipid metabolism and phagocytic function. Further research is warranted to explore the potential applications of Paeonol and to elucidate the molecular mechanisms underlying the observed effects. Frontiers Media S.A. 2023-06-28 /pmc/articles/PMC10338837/ /pubmed/37456739 http://dx.doi.org/10.3389/fphar.2023.1214756 Text en Copyright © 2023 Miao, Liu, Liao, Li, Kuang, Zheng, Li and Lan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Miao, Jifei
Liu, Xiaoming
Liao, Yuanpin
Li, Yiwen
Kuang, Yingyan
Zheng, Juanxia
Li, Zigang
Lan, Jiao
Paeonol enhances macrophage phagocytic function by modulating lipid metabolism through the P53-TREM2 axis
title Paeonol enhances macrophage phagocytic function by modulating lipid metabolism through the P53-TREM2 axis
title_full Paeonol enhances macrophage phagocytic function by modulating lipid metabolism through the P53-TREM2 axis
title_fullStr Paeonol enhances macrophage phagocytic function by modulating lipid metabolism through the P53-TREM2 axis
title_full_unstemmed Paeonol enhances macrophage phagocytic function by modulating lipid metabolism through the P53-TREM2 axis
title_short Paeonol enhances macrophage phagocytic function by modulating lipid metabolism through the P53-TREM2 axis
title_sort paeonol enhances macrophage phagocytic function by modulating lipid metabolism through the p53-trem2 axis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338837/
https://www.ncbi.nlm.nih.gov/pubmed/37456739
http://dx.doi.org/10.3389/fphar.2023.1214756
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