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Adenosine triphosphate inhibits cytokine release from lipopolysaccharide-activated microglia via P2y receptors

Tadanori Ogata1, Miao Chuai, Tadao Morino

  • 1Department of Orthopaedic Surgery, School of Medicine, Ehime University, Shigenobu, Ehime 791-0295, Japan. ogata@m.ehime-u.ac.jp

Brain Research
|July 30, 2003
PubMed

Insights

Adenosine triphosphate (ATP) inhibits the release of inflammatory cytokines from activated microglia. This finding suggests that P2Y receptor agonists could be a potential treatment for spinal cord injuries and related conditions.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Microglial activation and proliferation are key responses to central nervous system injuries.
  • Understanding the molecular mechanisms regulating microglial inflammatory responses is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To investigate the effects of adenosine triphosphate (ATP) on lipopolysaccharide (LPS)-activated microglia from rat spinal cords.
  • To determine the role of purinergic receptors in mediating ATP's inhibitory effects on cytokine release.

Main Methods:

  • Cultured microglia from rat embryonic spinal cords were stimulated with LPS.
  • The release of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta, and interleukin-6 was measured.
  • The inhibitory effects of various endogenous purines (ATP, ADP, CTP, UDP, UTP) and P2Y receptor agonists (ADPbetaS, 2-methylthio-ATP) were assessed.

Main Results:

  • ATP significantly inhibited LPS-induced release of TNF-alpha, IL-1beta, and IL-6 in a dose-dependent manner.
  • The rank order of inhibitory potency for endogenous purines was ATP > ADP >> UTP > UDP > CTP.
  • Selective P2Y receptor agonists mimicked ATP's inhibitory effects, indicating a role for metabotropic purinergic receptors.

Conclusions:

  • ATP inhibits pro-inflammatory cytokine release from LPS-activated microglia via metabotropic P2Y receptors.
  • P2Y receptor agonists represent a potential therapeutic approach for managing spinal cord pathologies involving neuroinflammation.

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