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

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 virusimmortalized T cell line (MT-20rg) by long-term exposure to asbestos chrysotile-B (CB). In this study, transforming growth factor-ßl (TGF-ßl) knockdown using lentiviral vector-mediated RNA interference showed that MT-2Rst cells secreted increased levels of TGF-ßl, and acquired resistance to TGF-ßl-mediated growth inhibition. We showed that exposure of MT-20rg cells to CB activated the mitogenactivated protein kinases (MAPKs), ERK1/2, p38 and JNK1. Furthermore, TGF-ßl-knockdown cells and treatment with MAPK inhibitors revealed that MT-2Rst cells secreted a high level of TGF-ßl mainly through phosphorylation of p38. However, an Annexin V assay indicated that TGF-ßl 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-20rg cells to CB induces a regulatory T cell-like phenotype, suggesting that chronic exposure to asbestos leads to a state of immune suppression.

Original languageEnglish
Pages (from-to)2522-2532
Number of pages11
JournalInternational Journal of Oncology
Volume45
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

Deltaretrovirus
Adult T Cell Leukemia Lymphoma
Asbestos
Transforming Growth Factors
Serpentine Asbestos
T-Lymphocytes
Cell Line
Apoptosis
Annexin A5
Regulatory T-Lymphocytes
Protein Kinase Inhibitors
RNA Interference
Protein Kinases
Lung Neoplasms
Neoplasms
Phosphorylation
Phenotype
Growth

Keywords

  • Asbestos chrysotile
  • MAPK
  • SMAD

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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.

In: International Journal of Oncology, Vol. 45, No. 6, 2014, p. 2522-2532.

Research output: Contribution to journalArticle

Maeda, Megumi ; Chen, Ying ; Hayashi, Hiroaki ; Kumagai-Takei, Naoko ; Matsuzaki, Hidenori ; Lee, Suni ; Nishimura, Yasumitsu ; Otsuki, Takemi. / Chronic exposure to asbestos enhances TGF-β1 production in the human adult T cell leukemia virus-immortalized T cell line MT-2. In: International Journal of Oncology. 2014 ; Vol. 45, No. 6. pp. 2522-2532.
@article{82172db572dd41b7b159d9db4ce38a27,
title = "Chronic exposure to asbestos enhances TGF-β1 production in the human adult T cell leukemia virus-immortalized T cell line MT-2",
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 virusimmortalized T cell line (MT-20rg) by long-term exposure to asbestos chrysotile-B (CB). In this study, transforming growth factor-{\ss}l (TGF-{\ss}l) knockdown using lentiviral vector-mediated RNA interference showed that MT-2Rst cells secreted increased levels of TGF-{\ss}l, and acquired resistance to TGF-{\ss}l-mediated growth inhibition. We showed that exposure of MT-20rg cells to CB activated the mitogenactivated protein kinases (MAPKs), ERK1/2, p38 and JNK1. Furthermore, TGF-{\ss}l-knockdown cells and treatment with MAPK inhibitors revealed that MT-2Rst cells secreted a high level of TGF-{\ss}l mainly through phosphorylation of p38. However, an Annexin V assay indicated that TGF-{\ss}l 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-20rg cells to CB induces a regulatory T cell-like phenotype, suggesting that chronic exposure to asbestos leads to a state of immune suppression.",
keywords = "Asbestos chrysotile, MAPK, SMAD",
author = "Megumi Maeda and Ying Chen and Hiroaki Hayashi and Naoko Kumagai-Takei and Hidenori Matsuzaki and Suni Lee and Yasumitsu Nishimura and Takemi Otsuki",
year = "2014",
doi = "10.3892/ijo.2014.2682",
language = "English",
volume = "45",
pages = "2522--2532",
journal = "International Journal of Oncology",
issn = "1019-6439",
publisher = "Spandidos Publications",
number = "6",

}

TY - JOUR

T1 - Chronic exposure to asbestos enhances TGF-β1 production in the human adult T cell leukemia virus-immortalized T cell line MT-2

AU - Maeda, Megumi

AU - Chen, Ying

AU - Hayashi, Hiroaki

AU - Kumagai-Takei, Naoko

AU - Matsuzaki, Hidenori

AU - Lee, Suni

AU - Nishimura, Yasumitsu

AU - Otsuki, Takemi

PY - 2014

Y1 - 2014

N2 - 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 virusimmortalized T cell line (MT-20rg) by long-term exposure to asbestos chrysotile-B (CB). In this study, transforming growth factor-ßl (TGF-ßl) knockdown using lentiviral vector-mediated RNA interference showed that MT-2Rst cells secreted increased levels of TGF-ßl, and acquired resistance to TGF-ßl-mediated growth inhibition. We showed that exposure of MT-20rg cells to CB activated the mitogenactivated protein kinases (MAPKs), ERK1/2, p38 and JNK1. Furthermore, TGF-ßl-knockdown cells and treatment with MAPK inhibitors revealed that MT-2Rst cells secreted a high level of TGF-ßl mainly through phosphorylation of p38. However, an Annexin V assay indicated that TGF-ßl 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-20rg cells to CB induces a regulatory T cell-like phenotype, suggesting that chronic exposure to asbestos leads to a state of immune suppression.

AB - 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 virusimmortalized T cell line (MT-20rg) by long-term exposure to asbestos chrysotile-B (CB). In this study, transforming growth factor-ßl (TGF-ßl) knockdown using lentiviral vector-mediated RNA interference showed that MT-2Rst cells secreted increased levels of TGF-ßl, and acquired resistance to TGF-ßl-mediated growth inhibition. We showed that exposure of MT-20rg cells to CB activated the mitogenactivated protein kinases (MAPKs), ERK1/2, p38 and JNK1. Furthermore, TGF-ßl-knockdown cells and treatment with MAPK inhibitors revealed that MT-2Rst cells secreted a high level of TGF-ßl mainly through phosphorylation of p38. However, an Annexin V assay indicated that TGF-ßl 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-20rg cells to CB induces a regulatory T cell-like phenotype, suggesting that chronic exposure to asbestos leads to a state of immune suppression.

KW - Asbestos chrysotile

KW - MAPK

KW - SMAD

UR - http://www.scopus.com/inward/record.url?scp=84907702548&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907702548&partnerID=8YFLogxK

U2 - 10.3892/ijo.2014.2682

DO - 10.3892/ijo.2014.2682

M3 - Article

C2 - 25358858

AN - SCOPUS:84907702548

VL - 45

SP - 2522

EP - 2532

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 6

ER -