Uncoupling protein 2 modulates polarization and metabolism of human primary macrophages via glycolysis and the NF‑κB pathway

Lang,Liguo; Zheng,Dongju; Jiang,Qingjun; Meng,Ting; Ma,Xiaohu; Yang,Yang

doi:10.3892/etm.2023.12282

Uncoupling protein 2 modulates polarization and metabolism of human primary macrophages via glycolysis and the NF‑κB pathway

Authors:
- Liguo Lang
- Dongju Zheng
- Qingjun Jiang
- Ting Meng
- Xiaohu Ma
- Yang Yang
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Affiliations: Department of Cardiology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region 750001, P.R. China
Published online on: November 2, 2023 https://doi.org/10.3892/etm.2023.12282
Article Number: 583
Copyright: © Lang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Metabolic abnormalities, particularly the M1/M2 macrophage imbalance, play a critical role in the development of various diseases, leading to severe inflammatory responses. The present study aimed to investigate the role of uncoupling protein 2 (UCP2) in regulating macrophage polarization, glycolysis, metabolic reprogramming, reactive oxygen species (ROS) and inflammation. Primary human macrophages were first polarized into M1 and M2 subtypes, and these two subtypes were infected by lentivirus‑mediated UCP2 overexpression or knockdown, followed by enzyme‑linked immunosorbent assay, reverse transcription‑quantitative PCR, western blotting and flow cytometry to analyze the effects of UCP2 on glycolysis, oxidative phosphorylation (OXPHOS), ROS production and cytokine secretion, respectively. The results demonstrated that UCP2 expression was suppressed in M1 macrophages and increased in M2 macrophages, suggesting its regulatory role in macrophage polarization. UCP2 overexpression decreased macrophage glycolysis, increased OXPHOS, decreased ROS production, and led to the conversion of M1 polarization to M2 polarization. This process involved NF‑κB signaling to regulate the secretion profile of cytokines and chemokines and affected the expression of key enzymes of glycolysis and a key factor for maintaining mitochondrial homeostasis (nuclear respiratory factor 1). UCP2 knockdown in M2 macrophages exacerbated inflammation and oxidative stress by promoting glycolysis, which was attenuated by the glycolysis inhibitor 2‑deoxyglucose. These findings highlight the critical role of UCP2 in regulating macrophage polarization, metabolism, inflammation and oxidative stress through its effects on glycolysis, providing valuable insights into potential therapeutic strategies for macrophage‑driven inflammatory and metabolic diseases.

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