title: Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers.
abstract: Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. Based on our hypothesis in which continuous exposure to asbestos of immune cells cause reduction of antitumor immunity, the decrease of natural killer cell killing activity with reduction of NKp46 activating receptor expression, inhibition of cytotoxic T cell clonal expansion, reduced CXCR3 chemokine receptor expression and production of interferon-γ production in CD4+ T cells were reported using cell line models, freshly isolated peripheral blood immune cells from health donors as well as asbestos exposed patients such as pleural plaque and mesothelioma. In addition to these findings, regulatory T cells (Treg) showed enhanced function through cell-cell contact and increased secretion of typical soluble factors, interleukin (IL)-10 and transforming growth factor (TGF)-β, in a cell line model using the MT-2 human polyclonal T cells and its sublines exposed continuously to asbestos fibers. Since these sublines showed a remarkable reduction of FoxO1 transcription factor, which regulates various cell cycle regulators in asbestos-exposed sublines, the cell cycle progression in these sublines was examined and compared with that of the original MT-2 cells. Results showed that cyclin D1 expression was markedly enhanced, and various cyclin-dependent kinase-inhibitors were reduced with increased S phases in the sublines. Furthermore, the increase of cyclin D1 expression was regulated by FoxO1. The overall findings indicate that antitumor immunity in asbestos-exposed individuals may be reduced in Treg through changes in the function and volume of Treg.
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Suni
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Matsuzaki
authors.affiliation: Department of Biofunctional Chemistry, Division of Bioscience, Okayama University Graduate School of Natural Science and Technology, Kita-Ku, Okayama 700-8530, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Maeda
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kumagai-Takei
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Tamayo
authors.initials: T
authors.lastname: Hatayama
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Yoshitome
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Takemi
authors.initials: T
authors.lastname: Otsuki
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D019938:Cyclin D1 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D000071161:Forkhead Box Protein O1 / Q000096:biosynthesis* / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D008654:Mesothelioma / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D000086002:Mesothelioma, Malignant; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D054367:Receptors, CXCR3 / Q000096:biosynthesis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000097:blood / Q000276:immunology
chemical_list: C515187:CXCR3 protein, human; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; C508609:IL10 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D054367:Receptors, CXCR3; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D019938:Cyclin D1