Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell

Our plain-English summary of Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell, by M. Maeda, S. Yamamoto, Y. Chen, et al (The Science of the Total Environment, 2012).

The study

• Authors: M. Maeda, S. Yamamoto, Y. Chen, N. Kumagai-Takei, H. Hayashi, H. Matsuzaki, S. Lee, T. Hatayama, N. Miyahara, M. Katoh, J. Hiratsuka, Y. Nishimura, T. Otsuki
• Journal: The Science of the Total Environment
• Published: 2012;429:174-82
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We have been investigating the immunological effects of asbestos. The establishment of a low-dose and continuously exposed human T cell line, HTLV-1 immortalized MT-2, to chrysotile (CB) revealed reduction of CXCR3 chemokine receptor and production of IFN-γ that caused a decline of tumor immunity. These effects were coupled with upregulation of IL-10, TGF-β, and BCL-2 in asbestos-exposed patients. To observe the immunological effects of crocidolite (CR) on human T cells, a trial to establish a low-dose and continuously exposed model was conducted and compared with a previously reported CB-exposed model (MT-2CB). Transient exposure of MT-2 original cells to CB or CR induced a similar level of apoptosis and growth inhibition. The establishment of a continuously exposed subline to CR (MT-2CR) revealed resistance against CR-induced apoptosis and upregulation of the BCL-2/BAX ratio similar to that recorded for MT-2CB. Both sublines showed reduced production of IFN-γ, TNF-α, and IL-6 with increased IL-10. cDNA microarray with network/pathway analyses focusing on transcription factors revealed that many similar factors related to cell proliferation were involved following continuous exposure to asbestos in both MT-2CB and MT-2CR. These results indicate that both CB and CR fibers affect human T cells with similar degrees even though the carcinogenic activity of these substances differs due to their chemical and physical forms. Trials to identify early detection markers for asbestos exposure or the occurrence of asbestos-inducing malignancies using these findings may lead to the development of clinical tools for asbestos-related diseases and chemoprevention that modifies the reduced tumor immunity.

Copyright © 2012 Elsevier B.V. All rights reserved.

In plain English

This was a laboratory study on a human T cell line called MT-2, a type of immune cell grown in culture. It was not a study of people. The authors compared chrysotile-B with crocidolite, both UICC standard asbestos samples. When the cells were briefly exposed to either fiber, their growth slowed and more of them died by apoptosis (programmed cell death), with more death at higher doses. At the same weight dose, chrysotile caused more apoptosis than crocidolite. Crocidolite, but not chrysotile, raised production of reactive oxygen species. The authors then grew cells with crocidolite at 25 μg/ml for more than 8 months. These long-exposed cells resisted crocidolite-induced apoptosis, as chrysotile-exposed cells had done in the authors' earlier work. They also made more IL-10, less IFN-γ and less TNF-α, and had a higher BCL-2/BAX protein ratio. Gene-expression analysis found similar transcription factors in both exposed lines. The authors concluded that both fibers affect human T cells to similar degrees. They noted that dosing by weight makes direct comparison of the fibers difficult.

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 culture experiment comparing short-term and long-term exposure of a human T cell line to two asbestos types
• Who was studied: MT-2, an HTLV-1-immortalized polyclonal human T cell line. Three crocidolite-exposed sublines were established, and the article reports on one of them (MT-2CR), compared with one chrysotile-exposed subline (MT-2CB) from earlier work and with the original unexposed MT-2 cells.
• Exposure: UICC standard chrysotile-B and crocidolite obtained from the Japan Asbestos Association. Short-term exposure was at 0 to 100 μg/ml. Continuous exposure was 10 μg/ml chrysotile-B or 25 μg/ml crocidolite for more than 8 months. Iron content was 3.53% in chrysotile-B and 39.12% in crocidolite.
• Main results:
  • In original MT-2 cells, all fiber concentrations reduced growth, but statistical significance was found only for the 50 and 100 μg/ml chrysotile-B groups.
  • In original MT-2 cells, apoptosis rose with dose for both fibers. At the same dose, chrysotile-B caused more apoptosis than crocidolite by each detection method.
  • In original MT-2 cells, reactive oxygen species increased with crocidolite dose, but chrysotile-B did not produce this response.
  • The continuously crocidolite-exposed subline (MT-2CR), when re-exposed to crocidolite, showed fewer apoptotic cells than original MT-2 cells at the same concentrations.
  • Compared with original MT-2 cells, MT-2CR showed upregulated IL-10 and decreased IFN-γ and TNF-α. Its IL-10 production was lower than that of MT-2CB.
  • The results section reported no significant differences in IL-6 production among the three cell lines.
  • In MT-2CR, bcl-2 and bax mRNA showed no substantial change. However, BCL-2 protein was significantly upregulated, and the BCL-2/BAX protein ratio was significantly higher than in original MT-2 cells.
  • Compared with original MT-2 cells, 2074 genes were uniquely altered in MT-2CB and 1970 in MT-2CR, with 650 altered in both. Network analysis found many similar transcription factors in both sublines.
• The authors' conclusion: The authors concluded that chrysotile and crocidolite affect human T cells to similar degrees, even though the two fibers differ in carcinogenic activity.
• Limitations the authors state:
  • Because doses were measured by weight and the fibers did not dissolve, the authors said it is difficult to claim chrysotile has a stronger apoptosis-inducing effect than crocidolite.
  • Fiber numbers and surface areas, rather than weight, may influence how much apoptosis occurs.
  • The microarray results showed only how many genes changed, not the roles of individual genes.

Topics

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

Medical terms in this study, explained in our Lexicon: Apoptosis, Crocidolite, Chrysotile, Carcinogenic, Asbestos Exposure.

Related studies

• Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells — Y. Miura, Y. Nishimura, et al. (2006)
• FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line — H. Matsuzaki, S. Lee, et al. (2016)
• Reduction of CXC chemokine receptor 3 in an in vitro model of continuous exposure to asbestos in a human T-cell line, MT-2 — M. Maeda, Y. Nishimura, et al. (2011)
• Apoptosis induced by crocidolite asbestos in human lung epithelial cells involves inactivation of Akt and MAPK pathways — A. Baldys, P. Pande, et al. (2007)
• Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos — M. Maeda, Y. Chen, et al. (2013)
• Inhibitory effects of anti-oxidants on apoptosis of a human polyclonal T-cell line, MT-2, induced by an asbestos, chrysotile-A — F. Hyodoh, A. Takata-Tomokuni, et al. (2005)

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