title: Chronic exposure to asbestos enhances TGF-β1 production in the human adult T cell leukemia virus-immortalized T cell line MT-2.
abstract: Asbestos exposure causes various tumors such as lung cancer and malignant mesothelioma. To elucidate the immunological alteration in asbestos-related tumors, an asbestos-induced apoptosis-resistant subline (MT-2Rst) was established from a human adult T cell leukemia virus-immortalized T cell line (MT-2Org) by long-term exposure to asbestos chrysotile-B (CB). In this study, transforming growth factor-β1 (TGF-β1) knockdown using lentiviral vector-mediated RNA interference showed that MT-2Rst cells secreted increased levels of TGF-β1, and acquired resistance to TGF-β1-mediated growth inhibition. We showed that exposure of MT-2Org cells to CB activated the mitogen-activated protein kinases (MAPKs), ERK1/2, p38 and JNK1. Furthermore, TGF-β1-knockdown cells and treatment with MAPK inhibitors revealed that MT-2Rst cells secreted a high level of TGF-β1 mainly through phosphorylation of p38. However, an Annexin V assay indicated that TGF-β1 resistance in MT-2Rst cells was not directly involved in the acquisition of resistance to apoptosis that is triggered by CB exposure. The overall results demonstrate that long-term exposure of MT-2Org cells to CB induces a regulatory T cell-like phenotype, suggesting that chronic exposure to asbestos leads to a state of immune suppression.
authors.affiliation: Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University, Okayama 7008530, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Maeda
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 7010192, Japan.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 7010192, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 7010192, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kumagai-Takei
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 7010192, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Matsuzaki
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 7010192, Japan.
authors.forename: Suni
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 7010192, Japan.
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama 7010192, Japan.
authors.forename: Takemi
authors.initials: T
authors.lastname: Otsuki
mesh_terms: D000328:Adult; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D001194:Asbestos / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000473:pathology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D017304:Annexin A5; D053773:Transforming Growth Factor beta1; D001194:Asbestos; D048051:p38 Mitogen-Activated Protein Kinases