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

Maeda,Megumi; Chen,Ying; Hayashi,Hiroaki; Kumagai-Takei,Naoko; Matsuzaki,Hidenori; Lee,Suni; Nishimura,Yasumitsu; Otsuki,Takemi

doi:10.3892/ijo.2014.2682

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

Authors:
- Megumi Maeda
- Ying Chen
- Hiroaki Hayashi
- Naoko Kumagai-Takei
- Hidenori Matsuzaki
- Suni Lee
- Yasumitsu Nishimura
- Takemi Otsuki
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Affiliations: Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University, Okayama 7008530, Japan, Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 7010192, Japan
Published online on: September 29, 2014 https://doi.org/10.3892/ijo.2014.2682
Pages: 2522-2532

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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.

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