title: Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell.
abstract: 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.
authors.affiliation: Department of Biofunctional Chemistry, Graduate School of Natural Science and Technology, Okayama University, 1-1-1 Tsushima-Naka, Okayama 700-8530, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Maeda
authors.forename: Shoko
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Naoko
authors.initials: N
authors.lastname: Kumagai-Takei
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Suni
authors.initials: S
authors.lastname: Lee
authors.forename: Tamayo
authors.initials: T
authors.lastname: Hatayama
authors.forename: Naomi
authors.initials: N
authors.lastname: Miyahara
authors.forename: Minako
authors.initials: M
authors.lastname: Katoh
authors.forename: Juni-Ichi
authors.initials: J
authors.lastname: Hiratsuka
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Takemi
authors.initials: T
authors.lastname: Otsuki
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D002461:Cell Line, Transformed; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D017638:Asbestos, Crocidolite