Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure

Megumi Maeda, Ying Chen, Suni Lee, Naoko Kumagai-Takei, Kei Yoshitome, Hidenori Matsuzaki, Shoko Yamamoto, Tamayo Hatayama, Miho Ikeda, Yasumitsu Nishimura, Takemi Otsuki

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)2024-2032
Number of pages9
JournalInternational Journal of Oncology
Volume50
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

Fingerprint

Interleukin-17
Asbestos
Blood Cells
Serpentine Asbestos
Natural Killer Cells
Cytotoxic T-Lymphocytes
Interferons
Immunity
CXCR3 Receptors
Natural Killer Cell Receptors
Cell Line
Ionomycin
Chemokine Receptors
Regulatory T-Lymphocytes
Helper-Inducer T-Lymphocytes
Coculture Techniques
T-Cell Antigen Receptor
Acetates
In Vitro Techniques

Keywords

  • Asbestos
  • CXCR3
  • IL-17
  • Interferon γ
  • Th17

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Maeda, M., Chen, Y., Lee, S., Kumagai-Takei, N., Yoshitome, K., Matsuzaki, H., ... Otsuki, T. (2017). Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure. International Journal of Oncology, 50(6), 2024-2032. https://doi.org/10.3892/ijo.2017.3991

Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure. / Maeda, Megumi; Chen, Ying; Lee, Suni; Kumagai-Takei, Naoko; Yoshitome, Kei; Matsuzaki, Hidenori; Yamamoto, Shoko; Hatayama, Tamayo; Ikeda, Miho; Nishimura, Yasumitsu; Otsuki, Takemi.

In: International Journal of Oncology, Vol. 50, No. 6, 01.06.2017, p. 2024-2032.

Research output: Contribution to journalArticle

Maeda, M, Chen, Y, Lee, S, Kumagai-Takei, N, Yoshitome, K, Matsuzaki, H, Yamamoto, S, Hatayama, T, Ikeda, M, Nishimura, Y & Otsuki, T 2017, 'Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure', International Journal of Oncology, vol. 50, no. 6, pp. 2024-2032. https://doi.org/10.3892/ijo.2017.3991
Maeda, Megumi ; Chen, Ying ; Lee, Suni ; Kumagai-Takei, Naoko ; Yoshitome, Kei ; Matsuzaki, Hidenori ; Yamamoto, Shoko ; Hatayama, Tamayo ; Ikeda, Miho ; Nishimura, Yasumitsu ; Otsuki, Takemi. / Induction of IL-17 production from human peripheral blood CD4+ cells by asbestos exposure. In: International Journal of Oncology. 2017 ; Vol. 50, No. 6. pp. 2024-2032.
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