Decrease in phosphorylation of ERK following decreased expression of NK cell-activating receptors in human NK cell line exposed to asbestos

Yasumitsu Nishimura, Megumi Maeda, N. Kumagai, H. Hayashi, Y. Miura, T. Otsuki

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

YT-CB5, which had been continuously cultured with chrysotile B (CB) asbestos, showed impaired cytotoxicity with decreased expression of NKG2D and 2B4 NK cell-activating receptors. In the present study, the phosphorylation of extracellular signal-regulated kinase (ERK), which is known to induce degranulation downstream of many NK cell-activating receptors, was examined in YT-CB5 by flow cytometry and compared with the control line YT-Org. YT-CB5 exhibited impaired phosphorylation of ERK1/2 induced by the recognition of K562 cells, downstream of a process mediated by Src family kinase and phosphoinositide 3-kinase. YT-CBS also exhibited impaired phosphorylation of ERK1/2 following incubation with K562 cells in the presence of anti-2B4 antibodies, where co-stimulation by 2B4 augmented the phosphorylation of ERK1/2 in YT-CB5 to a similar degree as in YT-Org. The phosphorylation of ERK1/2 induced by an inhibitor against phosphatase (PP) 1 and PP2A was also lower in YT-CB5 compared with YT-Org. Moreover, bead-bound antibodies to NKG2D, which contribute to cytotoxicity against K562 cells, induced negligible phosphorylation of ERK1/2 in YT-CB5, although antibodies to 2B4. induced a comparatively greater level of phosphorylation. Additionally, peripheral blood (PB-) NK cells with low expression of NKG2D showed lower phosphorylation of ERK1/2 mediated by anti-NKG2D antibodies compared with PB-NK cells with high expression of NKG2D. These results indicate that signal transduction events leading to the phosphorylation of ERK is impaired in YT-CB5 due to decreased expression of NKG2D. Further studies are required to clarify whether this suppressive effect of asbestos exposure on NK cells might promote lung cancer and mesothelioma in people who have inhaled asbestos.

Original languageEnglish
Pages (from-to)879-888
Number of pages10
JournalInternational Journal of Immunopathology and Pharmacology
Volume22
Issue number4
Publication statusPublished - Oct 2009
Externally publishedYes

Fingerprint

Natural Killer Cell Receptors
Asbestos
Extracellular Signal-Regulated MAP Kinases
Natural Killer Cells
Phosphorylation
Cell Line
K562 Cells
Anti-Idiotypic Antibodies
Blood Cells
Serpentine Asbestos
1-Phosphatidylinositol 4-Kinase
src-Family Kinases
Antibodies
Mesothelioma
Signal Transduction
Lung Neoplasms
Flow Cytometry

Keywords

  • Asbestos
  • ERK
  • Natural killer cell
  • NK cell-activating receptor

ASJC Scopus subject areas

  • Pharmacology
  • Immunology
  • Immunology and Allergy

Cite this

Decrease in phosphorylation of ERK following decreased expression of NK cell-activating receptors in human NK cell line exposed to asbestos. / Nishimura, Yasumitsu; Maeda, Megumi; Kumagai, N.; Hayashi, H.; Miura, Y.; Otsuki, T.

In: International Journal of Immunopathology and Pharmacology, Vol. 22, No. 4, 10.2009, p. 879-888.

Research output: Contribution to journalArticle

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