FullText URL ijo_50_1_66.pdf
Author Lee, Suni| Matsuzaki, Hidenori| Maeda, Megumi| Yamamoto, Shoko| Kumagai-Takei, Naoko| Hatayama, Tamayo| Ikeda, Miho| Yoshitome, Kei| Nishimura, Yasumitsu| Otsuki, Takemi|
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.
Note This is an article published by Spandidos Publications
Published Date 2016-11-22
Publication Title International Journal of Oncology
Volume volume50
Issue issue1
Publisher Spandidos
Start Page 66
End Page 74
ISSN 1019-6439
NCID AA10992511
Content Type Journal Article
language 英語
OAI-PMH Set 岡山大学
Copyright Holders https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
File Version publisher
PubMed ID 27878235
DOI 10.3892/ijo.2016.3776
Web of Sience KeyUT 000391419200007
Related Url https://doi.org/10.3892/ijo.2016.3776
FullText URL ijo_50_6_2024.pdf
Author Maeda, Megumi| Chen, Ying| Lee, Suni| Kumagai-Takei, Naoko| Yoshitome, Kei| Matsuzaki, Hidenori| Yamamoto, Shoko| Hatayama, Tamayo| Ikeda, Miho| Nishimura, Yasumitsu| Otsuki, Takemi|
Abstract We have previously reported that chronic, recurrent and low-dose exposure to asbestos fibers causes a reduction in antitumor immunity. Investigation of natural killer (NK) cells using an in vitro cell line model and comprising in vitro activation using freshly isolated NK cells co-cultured with chrysotile fibers, as well as NK cells derived from asbestos-exposed patients with pleural plaque (PP) or malignant mesothelioma (MM), revealed decreased expression of NK cell activating receptors such as NKG2D, 2B4 and NKp46. An in vitro differentiation and clonal expansion model for CD8+ cytotoxic T lymphocytes (CTLs) showed reduced cytotoxicity with decreased levels of cytotoxic molecules such as granzyme B and perforin, as well as suppressed proliferation of CTLs. Additionally, analysis of T helper cells showed that surface CXCR3, chemokine receptor, and the productive potential of interferon (IFN)γ were reduced following asbestos exposure in an in vitro cell line model and in peripheral CD4+ cells of asbestos-exposed patients. Moreover, experiments revealed that asbestos exposure enhanced regulatory T cell (Treg) function. This study also focused on CXCR3 expression and the Th-17 cell fraction. Following activation with T-cell receptor and co-culture with various concentrations of chrysotile fibers using freshly isolated CD4+ surface CXCR3 positive and negative fractions, the intracellular expression of CXCR3, IFNγ and IL-17 remained unchanged when co-cultured with chrysotile. However, subsequent re-stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin resulted in enhanced IL-17 production and expression, particularly in CD4+ surface CXCR3 positive cells. These results indicated that the balance and polarization between Treg and Th-17 fractions play an important role with respect to the immunological effects of asbestos and the associated reduction in antitumor immunity.
Note This is an article published by Spandidos Publications This fulltext availavle in Nov 2017
Published Date 2017-05-09
Publication Title International Journal of Oncology
Volume volume50
Issue issue6
Publisher Spandidos
Start Page 2024
End Page 2032
ISSN 1019-6439
NCID AA10992511
Content Type Journal Article
language 英語
OAI-PMH Set 岡山大学
Copyright Holders https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
File Version publisher
PubMed ID 28498408
DOI 10.3892/ijo.2017.3991
Web of Sience KeyUT 000402692100010
Related Url https://doi.org/10.3892/ijo.2017.3991