Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250100, China; Department of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, United States.
Department of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, United States.
J Hazard Mater. 2024 Mar 15;466:133590. doi: 10.1016/j.jhazmat.2024.133590. Epub 2024 Jan 23.
Mox macrophages were identified recently and are closely associated with atherosclerosis. Considering the potential health risks and the impact on macrophage modulation, this study investigated the Mox polarization of macrophages induced by nanoparticles (NPs) with tunable hydrophobicity. One nanoparticle (C4NP) with intermediate hydrophobicity efficiently upregulated the mRNA expression of Mox-related genes including HO-1, Srxn1, Txnrd1, Gsr, Vegf and Cox-2 through increased accumulation of Nrf2 at a nontoxic concentration in both resting and LPS-challenged macrophages. Additionally, C4NP impaired phagocytic capacity by 20% and significantly increased the secretion of cytokines, including TNFα, IL-6 and IL-10. Mechanistic studies indicated that intracellular reactive oxygen species (ROS) were elevated by 1.5-fold and 2.6-fold in resting and LPS-challenged macrophages respectively. Phosphorylated p62 was increased by 2.5-fold in resting macrophages and maintained a high level in LPS-challenged ones, both of which partially accounted for the significant accumulation of Nrf2 and HO-1. Notably, C4NP depolarized mitochondrial membrane potential by more than 50% and switched macrophages from oxidative phosphorylation-based aerobic metabolism to glycolysis for energy supply. Overall, this study reveals a novel molecular mechanism potentially involving ROS-Nrf2-p62 signaling in mediating macrophage Mox polarization, holding promise in ensuring safer and more efficient use of nanomaterials.
Mox 巨噬细胞最近被发现，与动脉粥样硬化密切相关。考虑到潜在的健康风险和对巨噬细胞调节的影响，本研究调查了具有可调疏水性的纳米颗粒（NPs）诱导的巨噬细胞 Mox 极化。一种具有中等疏水性的纳米粒子（C4NP）在非毒性浓度下通过增加 Nrf2 的积累，在静止和 LPS 刺激的巨噬细胞中有效地上调了 Mox 相关基因（包括 HO-1、Srxn1、Txnrd1、Gsr、Vegf 和 Cox-2）的 mRNA 表达。此外，C4NP 以非毒性浓度抑制吞噬能力 20%，并显著增加细胞因子的分泌，包括 TNFα、IL-6 和 IL-10。机制研究表明，C4NP 分别使静止和 LPS 刺激的巨噬细胞中的细胞内活性氧（ROS）增加了 1.5 倍和 2.6 倍。p62 的磷酸化在静止的巨噬细胞中增加了 2.5 倍，并在 LPS 刺激的巨噬细胞中保持高水平，这两者部分解释了 Nrf2 和 HO-1 的显著积累。值得注意的是，C4NP 使线粒体膜电位去极化超过 50%，并使巨噬细胞从基于氧化磷酸化的有氧代谢转变为糖酵解以提供能量。总的来说，这项研究揭示了一种新的分子机制，可能涉及 ROS-Nrf2-p62 信号通路，有望确保纳米材料更安全、更有效地使用。
