PKC θ-mediated Ca2+/NF-AT signalling pathway may be involved in T-cell immunosuppression in coal-burning arsenic-poisoned population

Environ Toxicol Pharmacol. 2017 Oct:55:44-50. doi: 10.1016/j.etap.2017.08.005. Epub 2017 Aug 12.

Abstract

Arsenic poisoning is a worldwide endemic disease that affects thousands of people. Growing evidence from animal, cell, and human studies indicates that arsenic has deleterious effects on the immune system. The present investigation is a population-based study that observed changes in the proliferation of human T-cells and IL-2 and INF-γ mRNA expression. Our results show that coal-burning arsenic can cause T-cell immunosuppression in the population, and participates in the occurrence and development of arsenic poisoning. In addition, we analyzed the intracellular calcium index, expression of protein kinase C theta (PKC θ) and phosphorylated PKC θ, and the DNA-binding activity of NF-AT in peripheral blood mononuclear cells (PBMCs). Our analysis demonstrates that the PKC θ-mediated Ca2+/NF-AT signalling pathway may be involved in the T-cell immunosuppression of coal-burning arsenic-poisoned population. This study provides important data for a mechanistic understanding of endemic arsenic poisoning.

Keywords: Arsenic poisoning; Coal; Immunosuppression; NF-AT; PKC θ.

MeSH terms

  • Adult
  • Arsenic Poisoning / genetics
  • Arsenic Poisoning / immunology*
  • Arsenic Poisoning / metabolism
  • Calcium / metabolism*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Coal / adverse effects*
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Interferon-gamma / genetics
  • Interleukin-2 / genetics
  • Male
  • Middle Aged
  • NFATC Transcription Factors / metabolism*
  • Phosphorylation / drug effects
  • Protein Kinase C-theta / metabolism*
  • Signal Transduction
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / drug effects

Substances

  • Coal
  • IFNG protein, human
  • IL2 protein, human
  • Interleukin-2
  • NFATC Transcription Factors
  • Interferon-gamma
  • PRKCQ protein, human
  • Protein Kinase C-theta
  • Calcium