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Published on: April 3, 2019

P2X7 receptor activation induces CXCL2 production in microglia through NFAT and PKC/MAPK pathways

Miho Shiratori1, Hidetoshi Tozaki-Saitoh, Mai Yoshitake

  • 1Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.

Journal of Neurochemistry
|May 19, 2010
PubMed

Insights

High ATP levels activate microglia via P2X7 receptors, increasing CXCL2 chemokine release through NFAT and MAPK pathways. This finding clarifies mechanisms in neuroinflammation and potential therapeutic targets.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are key immune cells in the central nervous system.
  • Microglial activation by extracellular ATP through P2 receptors releases inflammatory mediators.
  • Mechanisms of ATP-induced chemokine release from microglia remain unclear.

Purpose of the Study:

  • To investigate the signaling pathways involved in ATP-induced CXCL2 chemokine production in microglia.
  • To elucidate the role of P2X7 receptors in microglial responses to ATP.

Main Methods:

  • Microglial cell cultures treated with ATP and P2X7 receptor agonists/antagonists.
  • Analysis of CXCL2 mRNA expression and protein release.
  • Assessment of NFAT and MAPK signaling pathway activation using specific inhibitors.

Main Results:

  • High ATP concentrations induced CXCL2 mRNA expression and release in microglia.
  • P2X7 receptor activation was critical for ATP-induced CXCL2 production.
  • ATP stimulated NFAT and MAPK (p38, ERK, JNK) activation via P2X7R.
  • NFAT and protein kinase C/MAPK pathways were essential for CXCL2 expression.

Conclusions:

  • ATP-induced CXCL2 production in microglia is mediated by P2X7 receptor signaling.
  • Both NFAT and protein kinase C/MAPK pathways are crucial for this process.
  • Findings offer insights into neuroinflammatory mechanisms and potential therapeutic strategies targeting P2X7R.

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