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Updated: Mar 26, 2026
Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
Autophagy upregulation promotes macrophages to escape mesoporous silica nanoparticle (MSN)-induced NF-κB-dependent
Chen Xi1, Jie Zhou2, Shuzhang Du3
1Pharmaceutical Department, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, People's Republic of China.
Background:
Our previous studies (Int J Nanomed 10:22, 2015) have indicated that a single large dose of mesoporous silica nanoparticles (MSNs) can induce severe and selective nephrotoxicity, which is closely related to inflammation mediated by the NF-κB pathway. However, the effect of MSNs on other organs and the interactions of nanomaterials with biological systems remain rudimentary.
Objective:
This study aimed to clarify the biological behaviour and influence of MSNs on macrophages.
Methods:
The mice received a single intraperitoneal injection of a suspension of 150, 300 of 600 mg/kg MSNs, and RAW 264.7 cells were treated with MSNs at various concentrations and times. Cell viability was determined by MTT assay and LDH release assay. The NF-κB pathway and the target proinflammatory cytokines IL-1β and TNF-α were determined by western blotting or ELISA. Autophagy is considered as an emerging mechanism of nanomaterials. So the autophagic ultrastructural analysis, the determination of Beclin-1 and LC3 expression, and the calculation of LC3II dots were employed to verify autophagy activation. In addition, RNA interference, autophagy agonist and inhibitor were used to explore the role of autophagy in inflammation.
Results:
The results indicated that MSNs are internalized into macrophages and induce cytotoxicity in a dose- and time-dependent manner. The NF-κB pathway, IL-1β and TNF-α were induced and released by MSNs. The levels of Beclin-1 and LC3II dots were obviously up-regulated by MSNs, which indicated that autophagy was induced in the MSN-treated cells. Moreover, the enhanced autophagy can attenuate the inflammation mediated by the NF-κB pathway, whereas the inhibition of autophagy can contribute to inflammation.
Conclusions:
In summary, our results suggest that autophagy may be a possible protective factor in inflammation induced by MSNs in macrophages.
Insights
Mesoporous silica nanoparticles (MSNs) trigger inflammation in macrophages via the NF-κB pathway. However, enhanced autophagy induced by MSNs can protect against this inflammation, suggesting a potential therapeutic role.
Area of Science:
- Nanomedicine and Toxicology
- Cellular Biology and Immunology
Background:
- Previous research linked mesoporous silica nanoparticles (MSNs) to dose-dependent nephrotoxicity via NF-κB mediated inflammation.
- The broader impact of MSNs on other organs and their biological interactions require further elucidation.
Purpose of the Study:
- To investigate the biological behavior of MSNs within macrophages.
- To determine the influence of MSNs on macrophage inflammatory responses and cellular pathways.
Main Methods:
- MSNs were administered to mice and RAW 264.7 macrophage cells.
- Cell viability, NF-κB pathway activation, and pro-inflammatory cytokine (IL-1β, TNF-α) levels were assessed.
- Autophagy markers (Beclin-1, LC3) and ultrastructure were analyzed; RNA interference and pharmacological modulators explored autophagy's role in inflammation.
Main Results:
- MSNs were internalized by macrophages, causing dose- and time-dependent cytotoxicity.
- MSNs activated the NF-κB pathway and induced IL-1β and TNF-α release.
- MSNs upregulated autophagy markers (Beclin-1, LC3II), indicating autophagy induction.
- Increased autophagy attenuated MSNs-induced inflammation, while autophagy inhibition exacerbated it.
Conclusions:
- Autophagy activation plays a protective role against MSNs-induced inflammation in macrophages.
- Autophagy represents a potential therapeutic target for mitigating MSN-related inflammatory side effects.
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