title: Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos.
abstract: Among the various biological effects of asbestos such as fibrogenesis and carcinogenesis, we have been focusing on the immunological effects becausesilica (SiO(2)) and asbestos chemically is a mineral silicate of silica. Observations of the effects of asbestos on CD4+ T cells showed reduction of CXCR3 chemokine receptor and reduced capacity of interferon γ production. In particular, use of theHTLV-1 immortalized human T cell line, MT-2, and cDNA array analysis have helped to identify the modification of CXCR3. We investigated alteration of protein expression among MT-2 original cells that had no contact with asbestos, and six chrysotile-continuously exposed independent sublines using ProteinChip and two-dimensional gel electrophoresis (2DGE) assays. Further confirmation of the changes in protein expression due to asbestos exposure was obtained after the 2DGE method indicated protein modification of β-actin. β-actin was upregulated in mRNA, as were the levels of protein expression and phosphorylation. Moreover, a binding assay between cells and chrysotile showed that various molecules related to the cytoskeleton such as vimentin, myosin-9 and tubulin-β2, as well as β-actin, exhibited enhanced bindings in asbestos-exposed cells. The overall findings indicate that the cell surface cytoskeleton may play an important role in inducing the cellular changes caused by asbestos in immune cells, since fibers are not incorporated to the cells and how the alterations of cytoskeleton determined cell destiny to cause the reduction of tumor immunity is important to consider the biological effects of asbestos. Further studies to target several cytoskeleton-related molecules associated with the effects of asbestos will result in a better understanding of the immunological effects of asbestos and support the development of chemo-prevention to recover anti-tumor immunity in asbestos-exposed patients.
authors.affiliation: Laboratory of Functional Glycobiochemistry, Department of Biofunctional Chemistry, Division of Agricultural and Life Science, Graduate School of Environmental and Life Science, Okayama University, 1-1-1 Tsushima-Naka, Okayama 700-8530, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Maeda
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: Jun-Ichi
authors.initials: J
authors.lastname: Hiratsuka
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kimura
authors.forename: Takemi
authors.initials: T
authors.lastname: Otsuki
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D017632:Asbestos, Serpentine / Q000633:toxicity*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002461:Cell Line, Transformed; D003598:Cytoskeletal Proteins / Q000276:immunology*; D003599:Cytoskeleton / Q000187:drug effects* / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D046228:Microarray Analysis; D009218:Myosins / Q000235:genetics / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000235:genetics / Q000276:immunology; D014746:Vimentin / Q000235:genetics / Q000276:immunology
chemical_list: D000199:Actins; D017632:Asbestos, Serpentine; C515187:CXCR3 protein, human; D003598:Cytoskeletal Proteins; D054367:Receptors, CXCR3; D014404:Tubulin; D014746:Vimentin; D007371:Interferon-gamma; D009218:Myosins
keywords: Asbestos; Cytoskeleton; Protein expression; T cell; β-Actin