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Different signaling pathways inhibit DNA methylation activity and up-regulate IFN-gamma in human lymphocytes

Victoria Bonilla-Henao1, Raquel Martínez, Francisco Sobrino

  • 1Departamento de Bioquímica Médica y Biología Molecular, Facultad de Medicina y Hospital Universitario Virgen Macarena, Universidad de Sevilla, Spain.

Journal of Leukocyte Biology
|October 6, 2005
PubMed

Insights

Protein kinase C activators and phosphatase inhibitors down-regulate DNA methylation activity in immune cells. This inhibition correlates with increased interferon-gamma (IFN-gamma) gene expression, suggesting a novel regulatory mechanism.

Area of Science:

  • Immunology
  • Epigenetics
  • Molecular Biology

Background:

  • DNA methylation plays a critical role in regulating immune cell function.
  • Understanding the modulation of DNA methylation is key to controlling immune responses.

Purpose of the Study:

  • To investigate the effects of specific chemical treatments on DNA methylation activity in immune cells.
  • To explore the correlation between altered DNA methylation and the expression of the interferon-gamma (IFN-gamma) gene.

Main Methods:

  • Incubation of Jurkat T cells and peripheral lymphocytes with protein kinase C activators and phosphatase inhibitors.
  • Dose-dependent analysis of DNA methylation activity.
  • Assessment of DNA methyltransferase mRNA and protein expression.
  • Evaluation of interferon-gamma (IFN-gamma) gene expression.
  • Treatment with sulfhydryl reagents to assess their impact on DNA methylation and IFN-gamma expression.

Main Results:

  • Short-time incubation with protein kinase C activators or phosphatase inhibitors dose-dependently down-regulated DNA methylation activity.
  • This down-regulation of DNA methylation correlated with the induction of interferon-gamma (IFN-gamma) gene expression.
  • No significant decrease in DNA methyltransferase mRNA or protein levels was observed post-treatment.
  • Sulfhydryl reagents strongly inhibited DNA methylation activity and induced IFN-gamma gene expression.

Conclusions:

  • Protein kinase C activators and phosphatase inhibitors can modulate DNA methylation activity in immune cells.
  • A link exists between the inhibition of DNA methylation and the induction of IFN-gamma gene expression.
  • Sulfhydryl reagents may represent a novel class of compounds influencing both DNA methylation and immune gene expression.

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