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Selenium nanoparticles efficiently inhibit M1 macrophage polarization by regulating selenoprotein to scavenge ROS in
Xiaoyan Zhong1, Yang Yang2, Limei Jian1
1The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, PR China.
Abstract:
Excessive reactive oxygen and nitrogen species (RONS) in the rheumatoid arthritis (RA) microenvironment act as key functional signaling molecules that induce M1 polarization of synovial macrophages, leading to an imbalance in the M1/M2 macrophage ratio and accelerating RA progression. Our previous studies found that selenium nanoparticles (Se NPs) effectively alleviate RA symptoms by scavenging intracellular RONS in macrophages. However, the mechanism by which Se NPs regulate macrophage polarization to inhibit RA progression remains unclear. Therefore, we synthesized stable spherical Se NPs. In vivo and in vitro studies found that Se NPs inhibited M1 macrophage polarization and suppressed inflammatory responses by scavenging ROS and suppressing lipid peroxidation to prevent ferroptosis, thereby alleviating RA progression. Further mechanism studies showed that Se NPs directly upregulate the expression of the selenoprotein GPx4 and simultaneously inhibit the expression of surface receptor molecules associated with the NF-κB signaling pathway in M1 macrophages. Thus, Se NPs enhance ROS scavenging efficiency by upregulating selenoprotein expression, which in turn blocks the NF-κB signaling pathway, effectively balancing between M1 and M2 macrophages by inhibiting the polarization of M1 macrophages, resulting in the alleviation of RA progression. This study provides necessary scientific evidence for the bioactivity of Se NPs and offers new strategies for the treatment of RA.
Insights
Selenium nanoparticles (Se NPs) reduce rheumatoid arthritis (RA) by inhibiting M1 macrophage polarization. This approach balances M1/M2 macrophages, reduces inflammation, and alleviates RA progression.
Area of Science:
- Biomedical Engineering
- Immunology
- Materials Science
Background:
- Rheumatoid arthritis (RA) involves M1 macrophage polarization driven by reactive oxygen and nitrogen species (RONS).
- Selenium nanoparticles (Se NPs) previously showed efficacy in alleviating RA by scavenging RONS.
Purpose of the Study:
- To elucidate the mechanism by which Se NPs regulate macrophage polarization in RA.
- To investigate Se NPs' potential as a therapeutic strategy for RA.
Main Methods:
- Synthesis of stable spherical selenium nanoparticles (Se NPs).
- In vivo and in vitro studies to assess Se NP effects on macrophage polarization and inflammatory responses.
- Mechanism studies involving gene and protein expression analysis (GPx4, NF-κB pathway).
Main Results:
- Se NPs inhibited M1 macrophage polarization and suppressed inflammation by scavenging reactive oxygen species (ROS) and preventing ferroptosis.
- Se NPs upregulated selenoprotein GPx4 expression and inhibited NF-κB signaling pathway components in M1 macrophages.
- Se NPs effectively alleviated RA progression in vivo and in vitro.
Conclusions:
- Se NPs balance M1/M2 macrophage ratios by inhibiting M1 polarization, offering a novel therapeutic strategy for RA.
- The mechanism involves enhanced ROS scavenging via GPx4 upregulation and NF-κB pathway blockade.
- This study validates the bioactivity of Se NPs for RA treatment.
