Active Oxygen Influences Foam Macrophage Formation by Regulating Peroxisome Proliferator-Activated Receptor-γ Expression
Abstract
Objective
To investigate the effect of reactive oxygen species (ROS) on foam macrophage formation by regulating the expression of peroxisome proliferator-activated receptor-γ (PPARγ).
Methods
From June 2018 to December 2021, human blood samples were obtained from 30 healthy donors, and peripheral blood mononuclear cells (PBMCs) were isolated. The PBMCs were differentiated into human monocyte-derived macrophages (HMDMs) and subsequently infected with Mycobacterium tuberculosis H37Ra strain to establish an in vitro human macrophage infection model. ROS production was modulated using N-acetylcysteine (NAC) and emodin, while PPARγ activity was regulated using the PPARγ agonist (BRL49653) or antagonist (GW9662). The effects of H37Ra infection on intracellular ROS production and lipid formation in macrophages, as well as the impact of ROS generation on foam macrophage formation, were assessed using 2', 7'-dichlorodihydrofluorescein diacetate (DCFH2-DA) and Oil Red O staining. The influence of ROS production on PPARγ expression in macrophages was examined by qRT-PCR and Western blot. Furthermore, the involvement of PPARγ activity in ROS-mediated regulation of foam macrophage formation was investigated by modulating PPARγ activity.
Results
The results of Oil Red O staining and DCFH2-DA detection showed that, compared with the control group, H37Ra infection promoted ROS production in HMDMs and induced foam cell formation, with statistically significant differences (P < 0.01). After treating HMDMs with NAC or emodin for 1 hour and then infecting with H37Ra, NAC treatment reduced intracellular ROS levels and lipid content, while emodin increased intracellular ROS levels and lipid content, both with statistically significant differences (P < 0.01). Western blot analysis indicated that H37Ra infection inhibited PPARγ production, NAC promoted PPARγ expression, and emodin inhibited PPARγ expression, with statistically significant differences (P < 0.05). Pre-treating HMDMs with BRL49653 or GW9662 for 1 hour before H37Ra infection showed that GW9662 promoted lipid accumulation in the cells, with statistically significant differences (P < 0.01).
Conclusion
ROS can promote the formation of foam macrophages by downregulating the expression of PPARγ.
Keywords: Foam macrophages, H37Ra, Reactive oxygen species, Peroxisome proliferator-activated receptor-γ
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