The biological effect of asbestos exposure is dependent on changes in iron homeostasis

Our plain-English summary of The biological effect of asbestos exposure is dependent on changes in iron homeostasis, by A.J. Ghio, J.M. Soukup, L.A. Dailey, et al (Inhalation Toxicology, 2016).

The study

• Authors: A.J. Ghio, J.M. Soukup, L.A. Dailey, J.H. Richards, H. Tong
• Journal: Inhalation Toxicology
• Published: 2016;28(14):698-705
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Functional groups on the surface of fibrous silicates can complex iron. We tested the postulate that (1) asbestos complexes and sequesters host cell iron resulting in a disruption of metal homeostasis and (2) this loss of essential metal results in an oxidative stress and biological effect in respiratory epithelial cells. Exposure of BEAS-2B cells to 50 μg/mL chrysotile resulted in diminished concentrations of mitochondrial iron. Preincubation of these cells with 200 μM ferric ammonium citrate (FAC) prevented significant mitochondrial iron loss following the same exposure. The host response to chrysotile included increased expression of the importer divalent metal transporter-1 (DMT1) supporting a functional iron deficiency. Incubation of BEAS-2B cells with both 200 μM FAC and 50 μg/mL chrysotile was associated with a greater cell accumulation of iron relative to either iron or chrysotile alone reflecting increased import to correct metal deficiency immediately following fiber exposure. Cellular oxidant generation was elevated after chrysotile exposure and this signal was diminished by co-incubation with 200 μM FAC. Similarly, exposure of BEAS-2B cells to 50 μg/mL chrysotile was associated with release of the proinflammatory mediators interleukin (IL)-6 and IL-8, and these changes were diminished by co-incubation with 200 μM FAC. We conclude that (1) the biological response following exposure to chrysotile is associated with complexation and sequestration of cell iron and (2) increasing available iron in the cell diminished the effects of asbestos exposure.

In plain English

This was a laboratory study of human airway cells grown in dishes, not a study of people or animals. Researchers at the US Environmental Protection Agency exposed an established line of human bronchial lining cells (BEAS-2B) to chrysotile asbestos. They chose chrysotile because its ideal chemical formula contains no iron. In a test without cells, chrysotile bound iron but not zinc from solution. In the cells, a 15-minute chrysotile exposure lowered iron in the mitochondria, the parts of the cell that produce energy. Giving the cells extra iron (ferric ammonium citrate) beforehand prevented this drop. After 24 hours, chrysotile increased the cells' main iron-import protein, DMT1, and its RNA rose 2.3 ± 0.6-fold. Cells given both chrysotile and extra iron took up more iron and made more of the iron-storage protein ferritin than with either alone. Chrysotile also raised the cells' oxidant production and their release of two inflammatory signals, IL-6 and IL-8, and extra iron lessened both. The authors concluded that the biological effect of asbestos depended on the fiber binding the cell's iron. They noted it was not possible to conclude that iron and oxidative stress alone were responsible.

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) experiment on a cultured human airway cell line, with an additional test of chrysotile and metal solutions without cells
• Who was studied: BEAS-2B cells, an immortalized line of normal human bronchial epithelial (airway lining) cells. Each measurement had at least three replicates, and experiments were repeated at least twice. No human subjects or animals were studied.
• Exposure: Intermediate chrysotile asbestos from the NIEHS, given to cells for 15 minutes, 4 hours or 24 hours depending on the experiment. The dose is shown in the article text as '50 mg/mL', but the PubMed abstract gives 50 μg/mL, so the micro symbol appears to have been lost. Some cells were also given ferric ammonium citrate (FAC), shown as '200 mM' in the text and as 200 μM in the PubMed abstract. Rotenone, a mitochondrial inhibitor, was used in one oxidant test.
• Main results:
  • In solution without cells, chrysotile bound iron but not zinc. When both metals were present, chrysotile favored iron.
  • In BEAS-2B cells exposed to chrysotile for 15 minutes, iron in the mitochondrial fraction decreased significantly, while iron in the nuclear fraction (which contained the spun-down fibers) increased.
  • In cells given extra iron (FAC) before chrysotile, mitochondrial iron did not decrease.
  • After 24 hours of chrysotile exposure, the iron importer DMT1 increased at the protein level, and DMT1 RNA increased 2.3 ± 0.6-fold.
  • Cells exposed to both chrysotile and FAC accumulated more iron than cells exposed to either one alone.
  • After 24 hours, the iron-storage protein ferritin rose in cells exposed to FAC or chrysotile, and was highest when both were given.
  • Oxidant generation by the cells increased after chrysotile exposure and was reduced by pretreatment with FAC.
  • Pretreatment with rotenone reduced oxidant generation after chrysotile. The authors took this to imply that part of the oxidant production came from mitochondria.
  • A 24-hour chrysotile exposure increased the cells' release of the inflammatory mediators IL-6 and IL-8.
  • Treating the cells with FAC reduced the chrysotile-induced increases in IL-6 and IL-8.
• The authors' conclusion: The authors concluded that the biological effect of asbestos was dependent on the fiber binding (complexing) the cell's own iron. In their view, the cells responded to this functional iron deficiency by increasing iron import, and oxidant generation and inflammatory signals depended on how much iron was available. They suggested, without testing amphiboles in this study, that this might help explain greater effects of amphibole asbestos relative to chrysotile.
• Limitations the authors state:
  • Although iron pretreatment reduced the IL-6 and IL-8 response, the authors stated it was not possible to conclude that iron and oxidative stress alone were responsible. They assumed other cell signaling was also involved.

Topics

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

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Silicate, Oxidative Stress, Chrysotile.

Related studies

• Disruption of iron homeostasis in mesothelial cells after talc pleurodesis — A.J. Ghio, J.M. Soukup, et al. (2012)
• Iron homeostasis in the lung following asbestos exposure — A.J. Ghio, J. Stonehuerner, et al. (2008)
• The role of iron in Libby amphibole-induced acute lung injury and inflammation — J.H. Shannahan, A.J. Ghio, et al. (2011)
• Synchrotron X-ray microscopy reveals early calcium and iron interaction with crocidolite fibers in the lung of exposed mice — L. Pascolo, G. Zabucchi, et al. (2016)
• The role of single nucleotide polymorphisms related to iron homeostasis in mesothelioma susceptibility after asbestos exposure: a genetic study on autoptic samples — P. Grignani, S.D. Visonà, et al. (2023)
• Commentary: The role of single nucleotide polymorphisms related to iron homeostasis in mesothelioma susceptibility after asbestos exposure: a genetic study on autoptic samples — G. Tagarakis, F. Tsolaki, et al. (2024)

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