Chrysotile Causes Human Bronchial Epithelial Cell Apoptosis in Response to the Fas-Mediated Apoptosis Pathway

Our plain-English summary of Chrysotile Causes Human Bronchial Epithelial Cell Apoptosis in Response to the Fas-Mediated Apoptosis Pathway, by M. Zhang, J. Chen, Z. Jiang, et al (Pathobiology, 2017).

The study

• Authors: M. Zhang, J. Chen, Z. Jiang, L. Zhu, W. Wu, Y. Xiao, K. Chen
• Journal: Pathobiology
• Published: 2017;84(5):229-236
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: Asbestos is harmful to human health. However, the pathogenicity of chrysotile is a controversial matter. This study aimed to investigate the apoptosis of a human bronchial epithelial cell line (BEAS-2B) exposed to chrysotile that may function in part through the Fas death receptor pathway.

Methods: Cultured human BEAS-2B cells were treated with chrysotile and cell viability was evaluated by CCK-8 assay. The induction of cell apoptosis was evaluated by FACS analysis. mRNA expression levels of Fas, caspase-3, and caspase-8 were evaluated quantitatively by real-time PCR. The expression of Fas, caspase-3, and caspase-8 proteins were evaluated by Western blot. Meanwhile, cells were preincubated with various concentrations of anti-Fas antibody (CH11) and antagonistic anti-Fas antibody (ZB4).

Results: Chrysotile inhibits proliferation, induces apoptosis, and upregulates the expression of Fas, caspase-3, and caspase-8. The role of Fas as a regulator of chrysotile-induced apoptosis in BEAS-2B cells was tested by the prominent increase in and partial blockade of the apoptotic rate with CH11 and ZB4. When CH11 was pretreated, a synergistic effect was apparent on chrysotile-induced apoptosis and the mRNA and protein expression levels of Fas and cleaved caspase-3.

Conclusion: Chrysotile causes the apoptosis of BEAS-2B cells via the Fas death receptor pathway. The Fas-mediated apoptosis pathway plays an important role in chrysotile-induced apoptosis of BEAS-2B cells in vitro.

© 2017 S. Karger AG, Basel.

In plain English

This was a laboratory study of human cells grown in culture, not a study of people. The authors exposed a commercially available human bronchial epithelial cell line (BEAS-2B), the type of cell that lines the airways, to chrysotile asbestos. After 48 hours, 5, 10 and 20 μg/cm2 of chrysotile did not significantly reduce cell viability, while 40 and 100 μg/cm2 did. The authors then used 10 μg/cm2, which they called a nontoxic dose, and measured apoptosis, a form of programmed cell death. It did not rise significantly at 6 hours and rose by 6, 11 and 15% at 24, 48 and 72 hours. At 48 hours chrysotile raised levels of Fas, a 'death receptor'. An antibody that activates Fas (CH11) increased chrysotile-induced cell death. An antibody that blocks Fas (ZB4) lowered it only slightly, and this was not a statistically significant difference from chrysotile alone. The authors concluded that chrysotile can cause BEAS-2B cell death through the Fas pathway. They noted the blocking antibody's weak effect and suggested further tests to confirm Fas's role.

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 cell line
• Who was studied: A commercially available human bronchial epithelial cell line (BEAS-2B), obtained from the American Type Culture Collection. No human subjects or animals were studied.
• Exposure: Chrysotile from the Japan Fibrous Materials Research Association, suspended in water. Viability was tested at 5, 10, 20, 40 and 100 μg/cm2 for 48 h. Most experiments used 10 μg/cm2 for 6, 24, 48 and 72 h, some with a Fas-activating antibody (CH11) or a Fas-blocking antibody (ZB4).
• Main results:
  • At 48 h, cell viability fell significantly with 40 and 100 μg/cm2 of chrysotile, but not with 5, 10 or 20 μg/cm2. The authors used 10 μg/cm2 as the nontoxic dose for later experiments.
  • In cells treated with 10 μg/cm2 of chrysotile, apoptosis did not increase significantly at 6 h. It increased by 6, 11 and 15% at 24, 48 and 72 h.
  • Fas mRNA was higher in cells treated with 10 μg/cm2 of chrysotile for 48 h than in untreated cells. Fas protein showed the same tendency.
  • Pretreatment with the Fas-activating antibody CH11 increased chrysotile-induced apoptosis at 48 h.
  • The Fas-blocking antibody ZB4 (100 to 300 ng/mL) only slightly decreased chrysotile-induced apoptosis at 48 h, and the article states ZB4 did not significantly reduce it. At 300 ng/mL there was no significant difference from chrysotile alone at 6, 24, 48 or 72 h.
  • With chrysotile plus CH11 (500 ng/mL) for 48 h, mRNA and protein expression of Fas, caspase-3 and caspase-8 increased. Procaspase-3 and procaspase-8 protein levels decreased, and cleaved caspase-3 increased.
• The authors' conclusion: The authors concluded that chrysotile is able to cause BEAS-2B cell apoptosis through the Fas-mediated pathway.
• Limitations the authors state:
  • The Fas-blocking antibody had a low effect. The authors suggested that Fas or FADD siRNA be used in further studies to confirm the role of the Fas receptor.
  • The authors said the partial blocking may reflect other cell-death pathways triggered by chrysotile, too low a dose of ZB4, or cell death caused by fiber uptake.

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, Apoptosis, Synergistic Effect.

Related studies

• Asbestos causes apoptosis in alveolar epithelial cells: role of iron-induced free radicals — A. Aljandali, H. Pollack, et al. (2001)
• Distinct autophagy-apoptosis related pathways activated by Multi-walled (NM 400) and Single-walled carbon nanotubes (NIST-SRM2483) in human bronchial epithelial (16HBE14o-) cells — M. Ghosh, S. Murugadoss, et al. (2020)
• N-acetylcysteine prevents cytotoxic effects induced by man-made mineral fibers in a human bronchial epithelial cell line — M. Zhang, H. Xia, et al. (2018)
• Multi-walled carbon nanotubes directly induce epithelial-mesenchymal transition in human bronchial epithelial cells via the TGF-β-mediated Akt/GSK-3β/SNAIL-1 signalling pathway — M. Polimeni, G.R. Gulino, et al. (2016)
• Apoptosis induced by crocidolite asbestos in human lung epithelial cells involves inactivation of Akt and MAPK pathways — A. Baldys, P. Pande, et al. (2007)
• The c-Jun N-terminal kinase signaling pathway mediates chrysotile asbestos-induced alveolar epithelial cell apoptosis — P. Li, T. Liu, et al. (2015)

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