TY - JOUR
T1 - Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell
AU - Maeda, Megumi
AU - Yamamoto, Shoko
AU - Chen, Ying
AU - Kumagai-Takei, Naoko
AU - Hayashi, Hiroaki
AU - Matsuzaki, Hidenori
AU - Lee, Suni
AU - Hatayama, Tamayo
AU - Miyahara, Naomi
AU - Katoh, Minako
AU - Hiratsuka, Juni ichi
AU - Nishimura, Yasumitsu
AU - Otsuki, Takemi
N1 - Funding Information:
The authors thank the former members of our department, Drs. Yoshie Miura, Shuko Murakami, Fuminori Hyodoh, Akiko Takata-Tomokuni, and Ayako Ueki for their contribution and establishing the fundamental concepts of this investigation. Parts of this work were supported by Special Funds for Promoting Science and Technology ( H18-1-3-3-1 ), JSPS KAKENHI ( 22790550 , 22700933 , 20390178 , 20890270 , 19689153 , 19790431 , 19790411 , 18390186 , 16390175 and 09670500 ), the Takeda Science Foundation ( Tokutei Kenkyu Josei I, 2008 ), and Kawasaki Medical School Project grants ( 16-212S , 16-401N , 17-210S , 17-404M , 17-611O , 18-209T , 18-403 , 18-601 , 19-205Y , 19-506 , 19-407M , 19-603T , 20-412I , 20-210O , 20-109N , 20-402O , 20-410I , 20-410I , 21-401 and 21-107 ).
PY - 2012/7/1
Y1 - 2012/7/1
N2 - We have been investigating the immunological effects of asbestos. The establishment of a low-dose and continuously exposed human T cell line, HTLV-1 immortalized MT-2, to chrysotile (CB) revealed reduction of CXCR3 chemokine receptor and production of IFN-γ that caused a decline of tumor immunity. These effects were coupled with upregulation of IL-10, TGF-β, and BCL-2 in asbestos-exposed patients. To observe the immunological effects of crocidolite (CR) on human T cells, a trial to establish a low-dose and continuously exposed model was conducted and compared with a previously reported CB-exposed model (MT-2CB). Transient exposure of MT-2 original cells to CB or CR induced a similar level of apoptosis and growth inhibition. The establishment of a continuously exposed subline to CR (MT-2CR) revealed resistance against CR-induced apoptosis and upregulation of the BCL-2/BAX ratio similar to that recorded for MT-2CB. Both sublines showed reduced production of IFN-γ, TNF-α, and IL-6 with increased IL-10. cDNA microarray with network/pathway analyses focusing on transcription factors revealed that many similar factors related to cell proliferation were involved following continuous exposure to asbestos in both MT-2CB and MT-2CR. These results indicate that both CB and CR fibers affect human T cells with similar degrees even though the carcinogenic activity of these substances differs due to their chemical and physical forms. Trials to identify early detection markers for asbestos exposure or the occurrence of asbestos-inducing malignancies using these findings may lead to the development of clinical tools for asbestos-related diseases and chemoprevention that modifies the reduced tumor immunity.
AB - We have been investigating the immunological effects of asbestos. The establishment of a low-dose and continuously exposed human T cell line, HTLV-1 immortalized MT-2, to chrysotile (CB) revealed reduction of CXCR3 chemokine receptor and production of IFN-γ that caused a decline of tumor immunity. These effects were coupled with upregulation of IL-10, TGF-β, and BCL-2 in asbestos-exposed patients. To observe the immunological effects of crocidolite (CR) on human T cells, a trial to establish a low-dose and continuously exposed model was conducted and compared with a previously reported CB-exposed model (MT-2CB). Transient exposure of MT-2 original cells to CB or CR induced a similar level of apoptosis and growth inhibition. The establishment of a continuously exposed subline to CR (MT-2CR) revealed resistance against CR-induced apoptosis and upregulation of the BCL-2/BAX ratio similar to that recorded for MT-2CB. Both sublines showed reduced production of IFN-γ, TNF-α, and IL-6 with increased IL-10. cDNA microarray with network/pathway analyses focusing on transcription factors revealed that many similar factors related to cell proliferation were involved following continuous exposure to asbestos in both MT-2CB and MT-2CR. These results indicate that both CB and CR fibers affect human T cells with similar degrees even though the carcinogenic activity of these substances differs due to their chemical and physical forms. Trials to identify early detection markers for asbestos exposure or the occurrence of asbestos-inducing malignancies using these findings may lead to the development of clinical tools for asbestos-related diseases and chemoprevention that modifies the reduced tumor immunity.
KW - Apoptosis
KW - Asbestos
KW - Chrysotile
KW - Crocidolite
KW - T cell
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UR - http://www.scopus.com/inward/citedby.url?scp=84862250710&partnerID=8YFLogxK
U2 - 10.1016/j.scitotenv.2012.04.043
DO - 10.1016/j.scitotenv.2012.04.043
M3 - Article
C2 - 22608188
AN - SCOPUS:84862250710
VL - 429
SP - 174
EP - 182
JO - Science of the Total Environment
JF - Science of the Total Environment
SN - 0048-9697
ER -