What question did this study set out to answer?

To determine the role of the microglial P2Y12 receptor in mediating inflammasome activation and neuroinflammatory cytokine production in response to extracellular ADP.

September 24, 2019European Journal of Immunology

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

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Authors

TSTomonori SuzukiTokyo University of Agriculture KKKuniko KohyamaTokyo Institute of Psychiatry KMKengo MoriyamaTokyo Institute of Psychiatry

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Implication

In vitro study demonstrates that extracellular ADP stimulates inflammasome and NF-κB activation via P2Y12 in microglia, highlighting a potential therapeutic target for neuroinflammation.

Key Points

To determine the role of the microglial P2Y12 receptor in mediating inflammasome activation and neuroinflammatory cytokine production in response to extracellular ADP.
Assessed cultured microglia using pharmacological inhibition with the selective antagonist PSB0739, siRNA-mediated knockdown, or P2Y12 receptor gene deficiency.
Stimulated cells with ADP and ADP-βS alongside ATP to evaluate NF-κB signaling, mitochondrial membrane potential changes, caspase-1 activation, and cytokine expression.
Genetic ablation, siRNA knockdown, or pharmacological blockade of P2Y12 markedly suppressed microglial IL-1β mRNA expression, mature IL-1β release, and IL-6 production.
Extracellular ADP and ADP-βS augmented IL-1β and IL-6 release, amplified NF-κB activation, altered mitochondrial membrane potential in concert with ATP, and increased caspase-1-positive cell counts through P2Y12.

Cite This Study

Suzuki et al. (2019) studied this question.

synapsesocial.com/papers/6a19c2ece7f8932c5eeaa79b https://doi.org/10.1002/eji.201848013

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Implication

In vitro study demonstrates that extracellular ADP stimulates inflammasome and NF-κB activation via P2Y12 in microglia, highlighting a potential therapeutic target for neuroinflammation.

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

Discussion

Member takes

Implication

Key Points

Cite This Study

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

Discussion

Member takes

Implication

Key Points

Cite This Study

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