TY - JOUR
T1 - FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line
AU - Matsuzaki, Hidenori
AU - Lee, Suni
AU - Maeda, Megumi
AU - Kumagai-Takei, Naoko
AU - Nishimura, Yasumitsu
AU - Otsuki, Takemi
N1 - Funding Information:
The authors thank Ms. Tamayo Hatayama and Shoko Yamamoto for their technical support. This study was supported by JSPS KAKENHI Grant Number 23890237 and 25860471 and Kawasaki Medical School Project Grants 23-6, 24-4 and 25-67.
Publisher Copyright:
© 2016 Informa UK Limited trading as Taylor & Francis Group.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/3/31
Y1 - 2016/3/31
N2 - Asbestos is known to cause malignant mesothelioma and lung cancer. Recent studies implicate tumor immunity in the development of various tumors, including malignant mesothelioma. In order to establish an in vitro T-cell model to clarify the effects of long-term exposure of asbestos on tumor immunity, in this study, human T-cell line MT-2 cells were cultured with asbestos for longer than 8 months and the resultant cells (MT-2Rst) were assessed for the expression of forkhead transcription factor FoxO1. Gene expression analysis revealed that the amount of FoxO1 mRNA decreased after long-term exposure of the MT-2 cells to asbestos. In accordance with this reduction in FoxO1, pro-apoptotic Foxo1 target genes Puma, Fas ligand and Bim were also seen to be downregulated in MT-2Rst cells. Furthermore, shRNA-mediated knock-down of FoxO1 reduced the number of apoptotic parental MT-2 cells after treatment with asbestos. On the other hand, overexpression of FoxO1 did not affect asbestos-induced apoptosis in MT-2Rst cells. These results suggested that FoxO1 played an important role in regulating asbestos-induced apoptosis and confirmed the presence of multiple pathways regulating resistance to asbestos in MT-2Rst cells.
AB - Asbestos is known to cause malignant mesothelioma and lung cancer. Recent studies implicate tumor immunity in the development of various tumors, including malignant mesothelioma. In order to establish an in vitro T-cell model to clarify the effects of long-term exposure of asbestos on tumor immunity, in this study, human T-cell line MT-2 cells were cultured with asbestos for longer than 8 months and the resultant cells (MT-2Rst) were assessed for the expression of forkhead transcription factor FoxO1. Gene expression analysis revealed that the amount of FoxO1 mRNA decreased after long-term exposure of the MT-2 cells to asbestos. In accordance with this reduction in FoxO1, pro-apoptotic Foxo1 target genes Puma, Fas ligand and Bim were also seen to be downregulated in MT-2Rst cells. Furthermore, shRNA-mediated knock-down of FoxO1 reduced the number of apoptotic parental MT-2 cells after treatment with asbestos. On the other hand, overexpression of FoxO1 did not affect asbestos-induced apoptosis in MT-2Rst cells. These results suggested that FoxO1 played an important role in regulating asbestos-induced apoptosis and confirmed the presence of multiple pathways regulating resistance to asbestos in MT-2Rst cells.
KW - Apoptosis
KW - Asbestos
KW - FoxO1
KW - Regulatory T-cell
KW - Transcription factor
UR - http://www.scopus.com/inward/record.url?scp=84962054919&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962054919&partnerID=8YFLogxK
U2 - 10.3109/1547691X.2016.1143539
DO - 10.3109/1547691X.2016.1143539
M3 - Article
C2 - 27042963
AN - SCOPUS:84962054919
SN - 1547-691X
VL - 13
SP - 620
EP - 627
JO - Journal of Immunotoxicology
JF - Journal of Immunotoxicology
IS - 5
ER -
