Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells

Our plain-English summary of Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells, by Y. Miura, Y. Nishimura, H. Katsuyama, et al (Apoptosis, 2006).

The study

• Authors: Y. Miura, Y. Nishimura, H. Katsuyama, M. Maeda, H. Hayashi, M. Dong, F. Hyodoh, M. Tomita, Y. Matsuo, A. Uesaka, K. Kuribayashi, T. Nakano, T. Kishimoto, T. Otsuki
• Journal: Apoptosis
• Published: 2006;11(10):1825-35
• Cited by: 51 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

To analyze the possibility that immunological alteration in asbestos-related diseases (ARDs) such as asbestosis (ASB) and malignant mesothelioma (MM) may affect the progression of cancers, a human adult T cell leukemia virus-immortalized T cell line (MT-2Org) was continuously exposed to 10 mug/ml of chrysotile-B (CB), an asbestos. After at least 8 months of exposure, the rate of apoptosis in the cells became very low and the resultant subline was designated MT-2Rst. The MT-2Rst cells were characterized by (i) enhanced expression of bcl-2, with regain of apoptosis-sensitivity by reduction of bcl-2 by siRNA, (ii) excess IL-10 secretion and expression, and (iii) activation of STAT3 that was inhibited by PP2, a specific inhibitor of Src family kinases. These results suggested that the contact between cells and asbestos may affect the human immune system and trigger a cascade of biological events such as activation of Src family kinases, enhancement of IL-10 expression, STAT3 activation and Bcl-2 overexpression. This speculation was partially confirmed by the detection of elevated bcl-2 expression levels in CD4 + peripheral blood T cells from patients with MM compared with those from patients with ASB or healthy donors. Further studies will be required to verify the role of T cells with enhanced bcl-2 expression in tumor progression induced by asbestos exposure.

In plain English

This was a laboratory study of a human T-cell line called MT-2, plus a small comparison of blood cells from patients and healthy donors in Japan. Short-term exposure to chrysotile-B asbestos made MT-2 cells undergo apoptosis (programmed cell death), more so at higher doses and longer times. The authors then grew the cells continuously with 10 µg/ml of chrysotile-B for more than 8 months. The resulting subline, MT-2Rst, became resistant to asbestos-induced cell death. Compared with the original cells, MT-2Rst cells had about 10-fold higher bcl-2 and over 10-fold lower bax gene expression, released about two-fold more IL-10, and showed greater STAT3 activation. Blocking bcl-2 made them sensitive to asbestos again. In blood CD4+ T cells, bcl-2 expression was significantly higher in 17 malignant mesothelioma patients than in five healthy volunteers and in asbestosis patients. Asbestosis patients resembled healthy donors. The authors concluded that long-term, low-level asbestos exposure affects human immune cells. They said further studies are needed to verify the role of these T cells in tumor progression.

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-line experiment, with an additional comparison of gene expression in blood T cells from patients and healthy donors
• Who was studied: The HTLV-1-immortalized human T-cell line MT-2 (original line MT-2Org and the asbestos-resistant subline MT-2Rst). Also CD4+ T cells from the blood of 17 malignant mesothelioma patients, asbestosis patients (n = 9 in Fig. 7) and 5 healthy volunteers. Ethics approval came from Kawasaki Medical School, Hyogo College of Medicine and Okayama Rosai Hospital, Japan. Collection dates are not given.
• Exposure: Chrysotile-B asbestos added to cell cultures: 0 to 50 µg/ml for 2 to 4 days (short-term), and 10 µg/ml continuously for more than 8 months (long-term). The patients' asbestos exposure is not described in detail.
• Main results:
  • In short-term exposure, growth of MT-2 cells was markedly reduced at more than 10 µg/ml chrysotile-B, and the share of apoptotic cells rose with dose and time.
  • After more than 8 months of continuous exposure to 10 µg/ml chrysotile-B, the proportion of dying (TUNEL-positive) cells was very low compared with the original, never-exposed cells.
  • In MT-2Rst cells, bcl-2 mRNA was about 10-fold higher and bax mRNA over 10-fold lower than in the original MT-2Org cells.
  • When bcl-2 was reduced with siRNA, MT-2Rst cells exposed to 5 and 10 µg/ml chrysotile-B showed a significant reduction in growth, meaning they regained sensitivity.
  • Compared with MT-2Org cells, MT-2Rst cells released about two-fold less IFN-gamma, TNF-alpha and IL-6 and two-fold more IL-10.
  • MT-2Rst cells showed greater STAT3 expression and phosphorylation than MT-2Org cells.
  • PP2, an inhibitor of Src family kinases, reduced IL-10 gene expression in a dose-dependent manner in both cell lines.
  • bcl-2 expression in blood CD4+ T cells from 17 malignant mesothelioma patients was significantly higher than in five healthy volunteers and in asbestosis patients.
  • Asbestosis patients without clinical signs of a malignant tumor had bcl-2 expression in CD4+ T cells similar to healthy donors.
• The authors' conclusion: The authors concluded that long-term, low-level recurrent asbestos exposure affects human immune-competent cells. In their account, it activates Src family kinases, IL-10, STAT3 signaling and Bcl-2, while short-term, high-level exposure kills these cells by apoptosis. They suggested that MT-2Rst cells may act as regulatory T cells and may suppress tumor immunity, and said further studies are needed to verify the role of T cells with enhanced bcl-2 in tumor progression.
• Limitations the authors state:
  • The role of T cells with enhanced bcl-2 expression in asbestos-related tumor progression still needs to be verified by further studies.
  • The authors note that CD4+ T cells from patients with tumors not caused by asbestos may also show increased bcl-2, so the increase may not be specific to asbestos-related cancer.
  • The possibility that resistance came from long-term oxidative stress and increased antioxidant defenses was not tested.

Topics

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

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

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• FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line — H. Matsuzaki, S. Lee, et al. (2016)
• 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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