Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells

Yoshie Miura, Yasumitsu Nishimura, Hironobu Katsuyama, Megumi Maeda, Hiroaki Hayashi, Maolong Dong, Fuminori Hyodoh, Masafumi Tomita, Yoshinobu Matsuo, Ayuko Uesaka, Kozo Kuribayashi, Takashi Nakano, Takumi Kishimoto, Takemi Otsuki

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

To analyze the possibility that immunological alteration in asbestos-related diseases (ARDs) such as asbestosis (ASB) and malignant mesothelioma (MM) may affect the progression of cancers, a human adult T cell leukemia virus-immortalized T cell line (MT-2Org) was continuously exposed to 10 μg/ml of chrysotile-B (CB), an asbestos. After at least 8 months of exposure, the rate of apoptosis in the cells became very low and the resultant subline was designated MT-2Rst. The MT-2Rst cells were characterized by (i) enhanced expression of bcl-2, with regain of apoptosis-sensitivity by reduction of bcl-2 by siRNA, (ii) excess IL-10 secretion and expression, and (iii) activation of STAT3 that was inhibited by PP2, a specific inhibitor of Src family kinases. These results suggested that the contact between cells and asbestos may affect the human immune system and trigger a cascade of biological events such as activation of Src family kinases, enhancement of IL-10 expression, STAT3 activation and Bcl-2 overexpression. This speculation was partially confirmed by the detection of elevated bcl-2 expression levels in CD4 + peripheral blood T cells from patients with MM compared with those from patients with ASB or healthy donors. Further studies will be required to verify the role of T cells with enhanced bcl-2 expression in tumor progression induced by asbestos exposure.

Original languageEnglish
Pages (from-to)1825-1835
Number of pages11
JournalApoptosis
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 1 2006
Externally publishedYes

Keywords

  • Apoptosis
  • Asbestos
  • Bcl-2
  • IL-10
  • T cell

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

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