Reduction of CXC chemokine receptor 3 in an in vitro model of continuous exposure to asbestos in a human T-cell line, MT-2

Megumi Maeda, Yasumitsu Nishimura, Hiroaki Hayashi, Naoko Kumagai, Ying Chen, Shuko Murakami, Yoshie Miura, Jun Ichi Hiratsuka, Takumi Kishimoto, Takemi Otsuki

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Because patients with silicosis who are chronically exposed to silica particles develop not only pulmonary fibrosis, but alsocomplications involving autoimmune diseases such as rheumatoid arthritis and systemic sclerosis, exposure to asbestos may affect the human immune system. This immunologic effect may impair antitumor immune function because cancer complications such as lung cancer and malignant mesothelioma are found in patients exposed to asbestos. To elucidate the antitumor immune status caused by CD4 + T cells exposed to asbestos, an in vitro T-cell model of long-term and low-level exposure to chrysotile asbestos was established from a human adult T-cell leukemia virus-1-immortalized human polyclonal T cell line, MT-2, and the resulting six sublines showed resistance to asbestos-induced apoptosis after more than 8 months of continuous exposure. The results of DNA microarray analysis showed that the expression of 139 genes was altered by long-term and low-level exposure to asbestos, and the profile was almost similar among the six sublines when compared with the original MT-2 cells that had never been exposed to asbestos. Pathway and network analysis indicated a down-regulation of IFN-γ signaling and expression of CXC chemokine receptor 3 (CXCR3) in the sublines, whereas ELISA and flow cytometry analysis demonstrated a reduction in Th1-related IFN-γ production and cell-surface CXCR3 expression. These findings suggest that chronic exposure to asbestos may reduce antitumor immune status in CD4 + T cells, and that an in vitro T-cell model may be useful in identifying molecules related to the impairment of antitumor immune function.

Original languageEnglish
Pages (from-to)470-479
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume45
Issue number3
DOIs
Publication statusPublished - Sep 1 2011
Externally publishedYes

Keywords

  • Asbestos
  • CXCR3
  • IFN-γ
  • Malignant mesothelioma

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Reduction of CXC chemokine receptor 3 in an in vitro model of continuous exposure to asbestos in a human T-cell line, MT-2'. Together they form a unique fingerprint.

  • Cite this