FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line

Our plain-English summary of FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line, by H. Matsuzaki, S. Lee, M. Maeda, et al (Journal of Immunotoxicology, 2016).

The study

• Authors: H. Matsuzaki, S. Lee, M. Maeda, N. Kumagai-Takei, Y. Nishimura, T. Otsuki
• Journal: Journal of Immunotoxicology
• Published: 2016;13(5):620-7
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos is known to cause malignant mesothelioma and lung cancer. Recent studies implicate tumor immunity in the development of various tumors, including malignant mesothelioma. In order to establish an in vitro T-cell model to clarify the effects of long-term exposure of asbestos on tumor immunity, in this study, human T-cell line MT-2 cells were cultured with asbestos for longer than 8 months and the resultant cells (MT-2Rst) were assessed for the expression of forkhead transcription factor FoxO1. Gene expression analysis revealed that the amount of FoxO1 mRNA decreased after long-term exposure of the MT-2 cells to asbestos. In accordance with this reduction in FoxO1, pro-apoptotic Foxo1 target genes Puma, Fas ligand and Bim were also seen to be down-regulated in MT-2Rst cells. Furthermore, shRNA-mediated knock-down of FoxO1 reduced the number of apoptotic parental MT-2 cells after treatment with asbestos. On the other hand, over-expression of FoxO1 did not affect asbestos-induced apoptosis in MT-2Rst cells. These results suggested that FoxO1 played an important role in regulating asbestos-induced apoptosis and confirmed the presence of multiple pathways regulating resistance to asbestos in MT-2Rst cells.

In plain English

This laboratory study used MT-2, a line of human immune T-cells grown in culture, not people. In earlier work, the authors' group had grown MT-2 cells for a long period with low concentrations of chrysotile A, chrysotile B or crocidolite. This produced sub-lines that resisted asbestos-induced cell death (apoptosis). The authors measured FoxO1, a protein that helps switch on cell-death genes. In all the asbestos-exposed sub-lines, FoxO1 messenger RNA was 20–30% of the level in the original MT-2 cells, and FoxO1 protein was also lower. Three cell-death genes controlled by FoxO1 (Puma, Bim and Fas ligand) were reduced in the chrysotile A sub-line CA1. When FoxO1 was artificially lowered in the original cells, apoptosis after 24 hours of chrysotile A (printed as 25 mg/ml) fell to 50–70% of that in identically treated control cells. Restoring FoxO1 in CA1 cells did not increase apoptosis or change messenger RNA levels of the survival protein Bcl-2. The authors concluded that FoxO1 regulated asbestos-induced apoptosis in these cells. They also concluded that the loss of FoxO1, together with higher Bcl-2, contributed to the cells' resistance.

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 human T-cell line, using asbestos-exposed sub-lines, gene knockdown and gene over-expression
• Who was studied: MT-2, a polyclonal human T-cell line (described as immortalized with human adult leukemia virus-1), obtained from the JCRB cell bank in Osaka, Japan, and seven asbestos-exposed sub-lines (CA1–3, CB1–3 and CR) established in the authors' earlier studies; work done at Kawasaki Medical School, Japan; experiments performed in triplicate
• Exposure: Long-term culture with chrysotile A, chrysotile B or crocidolite (Union for International Cancer Control standard samples), at concentrations printed as 10 mg/ml for chrysotile A and chrysotile B and 25 mg/ml for crocidolite; in the apoptosis tests, cells were treated with chrysotile A at concentrations printed as 10 or 25 mg/ml for 24 hours
• Main results:
  • In all the asbestos-exposed MT-2 sub-lines, FoxO1 mRNA was 20–30% of the amount in the original (MT-2Org) cells, and FoxO1 protein was also reduced
  • mRNA of the FoxO1 target genes Puma, Bim and Fas ligand was decreased in the chrysotile A-exposed CA1 sub-line compared with the original cells
  • In the original MT-2 cells, lowering FoxO1 (shRNA knockdown) reduced the number of apoptotic cells after 24 hours of chrysotile A treatment (printed as 25 mg/ml) to 50–70% of control cells given the same treatment; it did not change background apoptosis levels
  • In CA1 cells, restoring FoxO1 did not increase the number of apoptotic cells after chrysotile A treatment
  • In CA1 cells, restored FoxO1 raised Puma mRNA. Bcl-2, measured as mRNA by real-time RT-PCR, was not affected by FoxO1 expression.
• The authors' conclusion: The authors concluded that FoxO1 regulated asbestos-induced apoptosis in MT-2 cells. They also concluded that down-regulation of FoxO1 signaling was implicated in the resistance to asbestos that the cells acquired after continuous exposure, alongside Bcl-2 over-expression.
• Limitations the authors state:
  • The authors stated that further analysis is needed to fully evaluate the role of FoxO1 down-regulation caused by asbestos

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Apoptosis, Malignant Mesothelioma, Lung Cancer.

Related studies

• Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers — S. Lee, H. Matsuzaki, et al. (2017)
• Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell — M. Maeda, S. Yamamoto, et al. (2012)
• 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)
• Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells — Y. Miura, Y. Nishimura, et al. (2006)
• Aberrant expression of FoxP3 in a human T cell line possessing regulatory T cell‑like function and exposed continuously to asbestos fibers — M. Maeda, H. Matsuzaki, et al. (2018)
• 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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