Synthetic hydrosilicate nanotubes induce low pro-inflammatory and cytotoxic responses compared to natural chrysotile in lung cell cultures

Our plain-English summary of Synthetic hydrosilicate nanotubes induce low pro-inflammatory and cytotoxic responses compared to natural chrysotile in lung cell cultures, by T. Skuland, T. Maslennikova, M. Låg, et al (Basic & Clinical Pharmacology & Toxicology, 2020).

The study

• Authors: T. Skuland, T. Maslennikova, M. Låg, E.M. Gatina, M.K. Serebryakova, A.S. Trulioff, I.V. Kudryavtsev, N. Klebnikova, I. Kruchinina, P.E. Schwarze, M. Refsnes
• Journal: Basic & Clinical Pharmacology & Toxicology
• Published: 2020;126(4):374-388
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos (Mg-hydrosilicate; chrysotile) is known to cause pleural diseases, pulmonary fibrosis and lung cancers, via mechanisms strongly depending on diameter-length ratio and possibly metal content. A critical question is whether synthetic hydrosilicate nanotubes (NTs) of short length possess little toxic potential compared to chrysotile. Five Mg- and two NiNTs of different lengths were assessed for cytotoxicity and pro-inflammatory responses in THP-1 macrophages and human bronchial epithelial lung cells (HBEC3-KT), in comparison with chrysotile. NT lengths/diameters were characterized by TEM, surface areas by BET- and BJH analysis, and chemical composition by XRD. The different Mg- and NiNTs induced little cytotoxicity in both cell models, in contrast to chrysotile that induced marked cytotoxicity. The two longest synthetic MgNTs, with median lengths of 3 and 5 µm, induced increased levels of pro-inflammatory cytokines in THP-1 macrophages, but much less than chrysotile (median length 15 µm) and silica nanoparticles (Si10). The shortest NTs did not induce any increase in cytokines. In HBEC3-KT cells, all synthetic NTs induced no or only small changes in cytokine responses, in contrast to chrysotile and Si10. The synthetic NTs induced lower TGF-β responses than chrysotile in both cell models. In conclusion, the pro-inflammatory responses were associated with the length of synthetic hydrosilicate NTs in THP-1 macrophages, but not in HBEC3-KT cells. Notably, the shortest NTs showed no or little pro-inflammatory activity or cytotoxicity in both cell models. Such a safety by design approach is important for development of new materials being candidates for various new products.

© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

In plain English

This laboratory study used human cells grown in culture. It compared man-made hydrosilicate nanotubes with natural chrysotile from Russia (median length 15 µm) and with silica nanoparticles. The authors made five magnesium tubes, chemically similar to chrysotile (median lengths 0.3 to 5 µm), and two nickel tubes (0.12 and 0.28 µm). Bronchial epithelial cells (HBEC3-KT) and THP-1 macrophages were exposed for 20 hours. Chrysotile clearly lowered cell survival; the synthetic tubes caused little or no reduction. In macrophages at 10.4 µg/cm2, the two longest magnesium tubes raised the inflammatory signal CXCL8 27- and 67-fold over unexposed cells, against 200-fold for chrysotile. Macrophage responses to the shortest magnesium tubes were small: two raised IL-1β 2.5-fold at the highest concentration, and a second viability test found small reductions. The chrysotile contained 3% to 4% iron oxides; the synthetic tubes did not. The authors concluded that only short synthetic tubes without contamination by metals such as iron are candidates for use. They noted they could not make tubes as long as chrysotile, and that complete in vivo testing should be considered.

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: in vitro (cell culture) experiment comparing synthetic Mg- and Ni-hydrosilicate nanotubes with natural chrysotile and silica nanoparticles (Si10, positive control)
• Who was studied: human bronchial epithelial HBEC3-KT cells and THP-1 monocytes differentiated into macrophage-like cells, obtained from the American Type Culture Collection; 3-6 independent biological replicates per test
• Exposure: five synthetic Mg-hydrosilicate nanotubes (median lengths 0.3-5 µm), two Ni-hydrosilicate nanotubes (0.12 and 0.28 µm), natural chrysotile from the Bazhenovskoe field, Russia (median 15 µm), and 10 nm silica nanoparticles, at 0-10.4 µg/cm2 for 20 hours
• Main results:
  • Median lengths: MgNT-1 to MgNT-5 were 0.3, 0.8, 2, 3 and 5 µm; NiNT-1 and NiNT-2 were 0.12 and 0.28 µm; chrysotile was 15 µm, with 95% above 5 µm
  • The natural chrysotile contained 3%-4% iron oxides and smaller amounts of NiO2 and TiO2, which were not present in the synthetic nanotubes
  • In HBEC3-KT epithelial cells, chrysotile reduced cell viability to approximately 60% at 2.6 µg/cm2 and 50% at 5.2 µg/cm2, while the Mg nanotubes caused no or only slight reductions
  • In THP-1 macrophages, none of the Mg or Ni nanotubes affected viability by the Alamar Blue assay, even at the highest concentrations
  • In THP-1 macrophages, a second viability test (flow cytometry) found small significant reductions with the three shortest Mg nanotubes (MgNT-1 to 3)
  • In THP-1 macrophages at 10.4 µg/cm2, the two longest Mg nanotubes (MgNT-4 and MgNT-5) increased CXCL8 27-fold and 67-fold
  • In THP-1 macrophages, chrysotile increased CXCL8 200-fold at 10.4 µg/cm2
  • In THP-1 macrophages at 10.4 µg/cm2, MgNT-1 and MgNT-2 (but not MgNT-3) caused a small (2.5-fold) but significant increase in IL-1β
  • In THP-1 macrophages at 10.4 µg/cm2, MgNT-4 and MgNT-5 increased IL-1β 17-fold and 62-fold, compared with 300-fold for chrysotile
  • The synthetic nanotubes caused lower TGF-β release than chrysotile in both cell types, though at the highest chrysotile concentration in THP-1 macrophages the response to NiNT-2 was similar to chrysotile
• The authors' conclusion: The authors concluded that only short synthetic nanotubes with no contamination by metals such as iron are relevant candidates for material applications using safe-by-design procedures
• Limitations the authors state:
  • The synthesis method could not produce synthetic Mg nanotubes as long as chrysotile, so the authors could not say whether tubes of equal length would be as active
  • This was a cell culture study; the authors stated that complete in vivo toxicity testing for acute and chronic exposure should be considered before commercial use

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Chrysotile, Pulmonary Fibrosis, Lung Cancer, Macrophage, Cytokine.

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