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Updated: Jan 19, 2026

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

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Extracellular ADP augments microglial inflammasome and NF-κB activation via the P2Y12 receptor

Tomonori Suzuki1,2, Kuniko Kohyama1, Kengo Moriyama1

  • 1Developmental Neuroimmunology Project, Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

European Journal of Immunology
|September 25, 2019
PubMed

Insights

Extracellular ADP activates the P2Y12 receptor on microglia, enhancing NLRP3 inflammasome activation and subsequent release of inflammatory cytokines like IL-1β and IL-6, contributing to neurological inflammation.

Area of Science:

  • Neuroimmunology
  • Molecular Biology
  • Inflammation Research

Background:

  • The NLRP3 inflammasome is a key mediator of inflammatory responses in neurological diseases.
  • Extracellular ATP activates NLRP3 inflammasome via the P2X7 receptor, but roles of other purinergic receptors in microglia remain unclear.
  • Microglia, the brain's immune cells, express various purinergic receptors, including the P2Y12 receptor.

Purpose of the Study:

  • To investigate the role of the microglial P2Y12 receptor in inflammasome-mediated inflammation.
  • To elucidate the signaling pathways involved in P2Y12 receptor-mediated microglial activation.

Main Methods:

  • In vitro studies using microglia.
  • Inhibition of P2Y12 receptor using PSB0739 and siRNA knockdown.
  • Measurement of IL-1β and IL-6 release and mRNA expression.
  • Assessment of NF-κB activation, mitochondrial membrane potential, and caspase-1 activation.

Main Results:

  • P2Y12 receptor inhibition or deficiency significantly suppressed IL-1β and IL-6 release from microglia.
  • Extracellular ADP and ADP-βS augmented IL-1β and IL-6 production, effects blocked by P2Y12 inhibition.
  • ADP-βS potentiated NF-κB activation, and ADP altered mitochondrial membrane potential and increased caspase-1 positive cells via P2Y12.

Conclusions:

  • Extracellular ADP acts through the P2Y12 receptor to enhance microglial inflammation.
  • This mechanism involves NF-κB activation and potentiation of the NLRP3 inflammasome pathway.
  • The P2Y12 receptor represents a novel target for modulating neuroinflammation.
Keywords:
IL-1βNF-κBNLRP3 inflammasomeP2Y12 receptor

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