Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos

Our plain-English summary of Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos, by M. Maeda, Y. Chen, N. Kumagai-Takei, et al (Immunobiology, 2013).

The study

• Authors: M. Maeda, Y. Chen, N. Kumagai-Takei, H. Hayashi, H. Matsuzaki, S. Lee, J. Hiratsuka, Y. Nishimura, Y. Kimura, T. Otsuki
• Journal: Immunobiology
• Published: 2013;218(9):1184-91
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Among the various biological effects of asbestos such as fibrogenesis and carcinogenesis, we have been focusing on the immunological effects becausesilica (SiO(2)) and asbestos chemically is a mineral silicate of silica. Observations of the effects of asbestos on CD4+ T cells showed reduction of CXCR3 chemokine receptor and reduced capacity of interferon γ production. In particular, use of theHTLV-1 immortalized human T cell line, MT-2, and cDNA array analysis have helped to identify the modification of CXCR3. We investigated alteration of protein expression among MT-2 original cells that had no contact with asbestos, and six chrysotile-continuously exposed independent sublines using ProteinChip and two-dimensional gel electrophoresis (2DGE) assays. Further confirmation of the changes in protein expression due to asbestos exposure was obtained after the 2DGE method indicated protein modification of β-actin. β-actin was upregulated in mRNA, as were the levels of protein expression and phosphorylation. Moreover, a binding assay between cells and chrysotile showed that various molecules related to the cytoskeleton such as vimentin, myosin-9 and tubulin-β2, as well as β-actin, exhibited enhanced bindings in asbestos-exposed cells. The overall findings indicate that the cell surface cytoskeleton may play an important role in inducing the cellular changes caused by asbestos in immune cells, since fibers are not incorporated to the cells and how the alterations of cytoskeleton determined cell destiny to cause the reduction of tumor immunity is important to consider the biological effects of asbestos. Further studies to target several cytoskeleton-related molecules associated with the effects of asbestos will result in a better understanding of the immunological effects of asbestos and support the development of chemo-prevention to recover anti-tumor immunity in asbestos-exposed patients.

Copyright © 2013 Elsevier GmbH. All rights reserved.

In plain English

This was a laboratory study of cells, not people. The authors used MT-2, a human T cell line, and six sublines that had been exposed in culture to chrysotile A (CA1 to CA3) or chrysotile B (CB1 to CB3) for more than eight months and had become resistant to chrysotile-induced cell death. They compared the proteins of these sublines with those of original MT-2 cells never exposed to asbestos. Protein profiling found more changed protein peaks in the cytosol and membrane fractions than in the nuclear fractions, with little difference between the two chrysotile types. The protein β-actin, part of the cell's internal skeleton (cytoskeleton), was identified as altered. All sublines, particularly the CB series, showed higher β-actin expression, and CB1 showed phosphorylated β-actin while the original cells did not. Proteins extracted from CB1 to CB3 bound chrysotile B more strongly than proteins from original cells at bands identified as myosin-9, vimentin, tubulin-β2 and β-actin. The authors concluded that the cell surface cytoskeleton may play an important role in asbestos-induced changes in immune cells. They added that how cytoskeletal changes produce these effects still needs clarification.

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) study using a human T cell line; protein analyses (ProteinChip, two-dimensional gel electrophoresis, RT-PCR, immunoblotting, binding assay)
• Who was studied: The HTLV-1 immortalized human T cell line MT-2. The study used the original line (never exposed to asbestos) and six sublines, CA1 to CA3 and CB1 to CB3, that had been established in the authors' earlier work. No human subjects were studied.
• Exposure: Continuous exposure for more than eight months to UICC standard chrysotile A (sublines CA1 to CA3) or chrysotile B (sublines CB1 to CB3). The article states that chrysotile A contained 2% fiber contamination with anthophyllite. Exposure started at a concentration printed as 10 per ml (the unit symbol is lost in the text). Sublines counted as established when about 80% of cells survived 50 to 100 per ml, a level at which more than 95% of original cells underwent apoptosis.
• Main results:
  • ProteinChip analysis, chrysotile A sublines compared with original cells: up- and down-regulated protein peaks numbered 12 and 6 in the cytosol fraction, 2 and 1 in the nuclear fraction, and 9 and 13 in the membrane fraction.
  • ProteinChip analysis, chrysotile B sublines compared with original cells: up- and down-regulated protein peaks numbered 11 and 7 in the cytosol fraction, 2 and 2 in the nuclear fraction, and 6 and 12 in the membrane fraction.
  • The authors concluded from these counts that continuous chrysotile exposure mainly altered protein expression in the cytosol and membrane fractions, not the nuclear fraction, with little difference between chrysotile A and chrysotile B.
  • Two-dimensional gel comparison of original cells and the CB1 subline showed spots of the same molecular weight but different isoelectric point. These spots were identified as β-actin.
  • β-actin mRNA and protein expression was higher in all six sublines than in original cells, particularly in the CB series. No numerical values are given in the text; the results are shown in figures.
  • The CB1 subline was positive for phosphorylated β-actin; original MT-2 cells were not.
  • In a binding assay, protein bands at 227, 53, 50 and 42 kDa from the chrysotile B-exposed sublines (CB1 to CB3) bound chrysotile B more than those from original cells. One band slightly below 75 kDa showed absence of binding in the sublines.
  • The four bands with increased binding were identified as myosin-9, vimentin, tubulin-β2 and β-actin, all cytoskeletal proteins.
• The authors' conclusion: The authors concluded that the cell surface cytoskeleton may play an important role in inducing the cellular changes caused by asbestos in immune cells, since the fibers are not taken into these cells.
• Limitations the authors state:
  • The authors state that it remains to be clarified how the increased expression of cytoskeleton-related molecules leads to changes inside the cell, which kinases and transcription factors are involved, and how CD4+ cell function changes.

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, Carcinogenesis, Silicate, Asbestos Exposure.

Related studies

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