Chronic exposure to asbestos enhances TGF-β1 production in the human adult T cell leukemia virus-immortalized T cell line MT-2

Our plain-English summary of Chronic exposure to asbestos enhances TGF-β1 production in the human adult T cell leukemia virus-immortalized T cell line MT-2, by M. Maeda, Y. Chen, H. Hayashi, et al (International Journal of Oncology, 2014).

The study

• Authors: M. Maeda, Y. Chen, H. Hayashi, N. Kumagai-Takei, H. Matsuzaki, S. Lee, Y. Nishimura, T. Otsuki
• Journal: International Journal of Oncology
• Published: 2014;45(6):2522-32
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos exposure causes various tumors such as lung cancer and malignant mesothelioma. To elucidate the immunological alteration in asbestos-related tumors, an asbestos-induced apoptosis-resistant subline (MT-2Rst) was established from a human adult T cell leukemia virus-immortalized T cell line (MT-2Org) by long-term exposure to asbestos chrysotile-B (CB). In this study, transforming growth factor-β1 (TGF-β1) knockdown using lentiviral vector-mediated RNA interference showed that MT-2Rst cells secreted increased levels of TGF-β1, and acquired resistance to TGF-β1-mediated growth inhibition. We showed that exposure of MT-2Org cells to CB activated the mitogen-activated protein kinases (MAPKs), ERK1/2, p38 and JNK1. Furthermore, TGF-β1-knockdown cells and treatment with MAPK inhibitors revealed that MT-2Rst cells secreted a high level of TGF-β1 mainly through phosphorylation of p38. However, an Annexin V assay indicated that TGF-β1 resistance in MT-2Rst cells was not directly involved in the acquisition of resistance to apoptosis that is triggered by CB exposure. The overall results demonstrate that long-term exposure of MT-2Org cells to CB induces a regulatory T cell-like phenotype, suggesting that chronic exposure to asbestos leads to a state of immune suppression.

In plain English

This laboratory study used a human T cell line, MT-2, immortalized by the adult T cell leukemia virus (HTLV-1). The authors compared the original cells (MT-2Org) with a subline (MT-2Rst) previously made resistant to asbestos-induced cell death by growing the cells with chrysotile-B asbestos (5 µg/cm2) for more than eight months. MT-2Rst cells released more TGF-β1, a protein that suppresses immune responses, into their culture fluid than the original cells did. TGF-β1 significantly slowed the growth of the original cells but not of MT-2Rst cells. When TGF-β1 was reduced in MT-2Rst cells by genetic knockdown, the growth-slowing effect returned. A drug blocking the enzyme p38 largely reduced TGF-β1 production by MT-2Rst cells. Reducing TGF-β1 did not remove the cells' resistance to asbestos-induced cell death. Short-term chrysotile-B exposure activated the signaling enzymes ERK1/2, p38 and JNK1 in the original cells, but the differences from untreated cells were not statistically significant. The authors concluded that long-term chrysotile-B exposure gave the cells features resembling regulatory T cells, suggesting that chronic asbestos exposure leads to immune suppression. The study used cells only, not people.

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 using an established asbestos-exposure model in a human T cell line
• Who was studied: Human HTLV-1-immortalized polyclonal T cell line MT-2 (original cells, MT-2Org), compared with an asbestos-resistant subline (MT-2Rst) derived from it. Some experiments used versions of MT-2Rst in which TGF-β1 had been knocked down. The work was done at institutions in Okayama, Japan. No human subjects were studied.
• Exposure: UICC standard chrysotile-B (CB) asbestos from Canada. Long-term exposure was 5 µg/cm2 for more than eight months, used to create MT-2Rst. Short-term exposure was 5, 12.5 or 25 µg/cm2 for 24 h.
• Main results:
  • TGF-β1 in culture fluid was higher for MT-2Rst cells than for MT-2Org cells. Intracellular TGF-β1 and TGF-β1 mRNA did not differ significantly between the two.
  • Added TGF-β1 significantly inhibited the growth of MT-2Org cells but did not inhibit MT-2Rst cells.
  • MT-2Rst cells with TGF-β1 knocked down were again growth-inhibited by TGF-β1. The authors interpreted this to mean that the resistance came through increased TGF-β1 production.
  • TGF-β receptor II mRNA was significantly lower in MT-2Rst cells. However, cell-surface TGF-βRII was low in both cell types, with no significant difference.
  • In MT-2Org cells, short-term chrysotile-B exposure was followed by phosphorylation (activation) of ERK1/2, p38 and JNK1. Differences from untreated controls were not statistically significant.
  • In MT-2Rst cells, the p38 inhibitor largely reduced TGF-β1 production. Inhibitors of ERK and JNK also decreased it.
  • MT-2Rst cells with TGF-β1 knocked down remained resistant to cell death caused by short-term, high-dose chrysotile-B, as did MT-2Rst control cells.
• The authors' conclusion: The authors concluded that long-term exposure of MT-2Org cells to chrysotile-B induces a regulatory T cell-like phenotype, suggesting that chronic asbestos exposure leads to a state of immune suppression.
• Limitations the authors state:
  • The authors stated that further study of regulatory T cells in mesothelioma patients is needed to clarify the immune suppression attributed to TGF-β1.

Topics

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

Related studies

• 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)
• Decrease in Intracellular Perforin Levels and IFN-γ Production in Human CD8+ T Cell Line following Long-Term Exposure to Asbestos Fibers — N. Kumagai-Takei, Y. Nishimura, et al. (2018)
• Increased production of matrix metalloproteinase-7 (MMP-7) by asbestos exposure enhances tissue migration of human regulatory T-like cells — S. Lee, S. Yamamoto, et al. (2021)
• Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos — M. Maeda, Y. Chen, et al. (2013)
• Podoplanin overexpression in human mesothelioma cell lines enhances the tumorigenic phenotype — E. Yamaki, T. Yajima, et al. (2013)
• FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line — H. Matsuzaki, S. Lee, et al. (2016)

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