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134 Pkc θ-mediated ca2+/nf-at signalling pathway may be involved in t-cell immunosuppression of coal-burning arsenic-poisoned population
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  1. QB Zeng,
  2. JY Gu,
  3. AH Zhang
  1. Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, Guizhou Medical University, Guiyang 550025, Guizhou, China

Abstract

Introduction 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 immune systems, but its specific mechanism needs to be further explored.

Methods This is a population-based study that observed the changes in the proliferation of human T cells, IL-2, and INF-γ mRNA expression of coal-burning arsenic-poisoned population and control population. In addition, the intracellular calcium index, expression of PKC θ and phosphorylated PKC θ, and the DNA binding activity of NF-AT in PBMCs were analysed.

Results In the exposure group, and the mild, moderate, and severe arsenic poisoning groups, the stimulation indexes of the T cells, the mRNA expression of IL-2 and INF-γ significantly reduce in comparison to the control group. A correlation analysis shows a clear correlation between PKC θ/NF-AT signalling, (Intracellular calcium index, PKC θ, p-PKC θ and the activity of the NF-AT binding DNA) T cell proliferation, and inflammatory factors (IL-2 and INF-γ).

Conclusion Coal-burning arsenic can cause T cell immunosuppression in the population, and participates in the occurrence and development of arsenic poisoning. In addition, the PKC θ-mediated Ca2+/NF-AT signalling pathway may be involved in the T-cell immunosuppression of the coal-burning arsenic poisoned population. The study provides important research data towards a mechanistic understanding of endemic arsenic poisoning. The next step should be to verify the results of this research in vitro and with a larger cohort.

Acknowledgements This work was supported by the Natural Science Foundations of China (81430077), and foundation at Guizhou Province for 2011 Collaborative Innovation Project [(2014)06].

  • Arsenic poisoning
  • Immunosuppression
  • Coal-burning

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