Size-dependent superparamagnetic iron oxide nanoparticles dictate interleukin-1β release from mouse bone marrow-derived macrophages

Our plain-English summary of Size-dependent superparamagnetic iron oxide nanoparticles dictate interleukin-1β release from mouse bone marrow-derived macrophages, by S. Chen, S. Chen, Y. Zeng, et al (Journal of Applied Toxicology, 2018).

The study

• Authors: S. Chen, S. Chen, Y. Zeng, L. Lin, C. Wu, Y. Ke, G. Liu
• Journal: Journal of Applied Toxicology
• Published: 2018;38(7):978-986
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely investigated for their biomedical applications in magnetic resonance imaging, targeting therapy, cell labeling, etc. It has been well documented that macrophages produce interleukin (IL)-1β via several signaling pathways, such as inflammasome activation in response to particles including silica, asbestos and urea crystals with lipopolysaccharide priming. However, the size and dose effects of SPIONs on macrophages and the mechanisms remain unclear. In this study, we explored the cytotoxicity and mechanisms of the synthesized SPIONs with different size distributions of 30, 80 and 120 nm, and compared their potential capability in inducing IL-1β release in mouse bone marrow-derived macrophages (BMMs). We found that SPIONs induced IL-1β release in a size- and dose-dependent manner, in which the smallest SPIONs triggered the highest IL-1β in BMMs. When cellular uptake of SPIONs was inhibited by the actin polymerization inhibitor, cytochalasin D, SPION-induced IL-1β release was suppressed in BMMs. Preventing lysosome damage with bafilomycin A1 or CA-074-Me also counteracted SPION-induced IL-1β release. Moreover, SPION-activated IL-1β release was also attenuated by reactive oxygen species scavengers, diphenylene iodonium or N-acetylcysteine. Our results elucidated the effects of size and dose on the cytotoxicity and mechanisms of IL-1β release of SPIONs on macrophages, which facilitate the theoretical and experimental application of SPIONs in biotechnology and biomedicine in the future.

Copyright © 2018 John Wiley & Sons, Ltd.

In plain English

This laboratory study did not test asbestos. Asbestos appears only as background, as one of several particles known to make immune cells release the inflammatory signal IL-1β when the cells are first primed with LPS, a bacterial substance. The authors made coated iron oxide nanoparticles (SPIONs, used in medical imaging) in three sizes, 30, 80 and 120 nm. They exposed macrophages, a type of immune cell grown from the bone marrow of female mice, to these particles. Without LPS priming, the cells released no IL-1β. Cell survival fell most with the smallest particles. In cells exposed for 24 hours without LPS priming, viability at 40 μg/ml was 13.57 ± 3.03% with 30 nm particles and 23.57 ± 1.15% with 80 nm particles, while toxicity of 120 nm particles was hardly detected. In LPS-primed cells, 30 nm particles caused the greatest IL-1β release. With 30 nm particles, release was significantly increased at 20 and 40 μg/ml. Blocking particle uptake, lysosome damage or reactive oxygen species reduced IL-1β release. The authors concluded that the effects depended on particle size and dose. They said a possible role of the NLRP3 inflammasome still needs to be confirmed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: laboratory (in vitro) cell experiment on mouse immune cells
• Who was studied: bone marrow-derived macrophages from eight-week-old female C57BL/6 mice obtained in Shanghai, China; number of mice not stated; results from three independent experiments
• Exposure: superparamagnetic iron oxide nanoparticles (SPIONs) coated with alkyl-polyethylenimine, in sizes of 30, 80 and 120 nm, at 2.5 to 40 μg/ml, with or without LPS priming; asbestos was not tested
• Main results:
  • In the 24-hour viability test without LPS priming, 30 nm SPIONs reduced cell viability to 24.49 ± 0.82% at 20 μg/ml and 13.57 ± 3.03% at 40 μg/ml
  • In the 24-hour viability test without LPS priming, 80 nm SPIONs were cytotoxic only at 40 μg/ml (viability 23.57 ± 1.15%); toxicity of 120 nm SPIONs was hardly detected
  • Cells treated with SPIONs alone, without LPS priming, did not produce IL-1β
  • In LPS-primed cells, 30 nm SPIONs reduced viability to 69.49 ± 1.08%, 17.80 ± 5.37% and 12.44 ± 0.61% at 10, 20 and 40 μg/ml
  • In LPS-primed cells, 80 nm SPIONs reduced viability to 67.07 ± 2.62% at 20 μg/ml and 31.57 ± 0.96% at 40 μg/ml; 120 nm SPIONs showed no detectable toxicity
  • In LPS-primed cells given 20 μg/ml, 30 nm SPIONs caused the greatest IL-1β release of the three sizes
  • In LPS-primed cells given 30 nm SPIONs, IL-1β release was significantly increased at 20 and 40 μg/ml
  • Blocking particle uptake with cytochalasin D significantly reduced IL-1β release for all three sizes
  • Agents that prevent lysosome damage (bafilomycin A1, CA-074-Me) counteracted IL-1β release
  • Reactive oxygen species inhibitors also suppressed IL-1β release: NAC partially and DPI significantly; TNF-α was also reduced by NAC or DPI
• The authors' conclusion: The authors concluded that SPIONs induced IL-1β release depending on size and dose, with the smallest particles causing the most. They linked this to particle uptake, lysosome damage and reactive oxygen species.
• Limitations the authors state:
  • The authors state that a possible role of the NLRP3 inflammasome in the cell death and IL-1β release was not shown and still needs to be confirmed

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Reactive Oxygen Species (ROS).

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