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P2Y(6) nucleotide receptor mediates monocyte interleukin-8 production in response to UDP or lipopolysaccharide

M Warny1, S Aboudola, S C Robson

  • 1Gastroenterology Divison, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. mwarny@caregroup.harvard.edu

The Journal of Biological Chemistry
|May 12, 2001
PubMed

Insights

Uridine diphosphate (UDP) activates interleukin-8 (IL-8) release in monocytic cells via the P2Y(6) receptor. Lipopolysaccharide also stimulates IL-8 production through P2Y(6) activation, highlighting its role in innate immunity.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Extracellular nucleotides act as signaling molecules through P2 nucleotide receptors.
  • The function of G protein-coupled P2Y receptors in monocytic cells remains largely unknown.
  • Monocytes play a crucial role in innate immune responses.

Purpose of the Study:

  • To investigate the role of P2Y(6) receptors in regulating chemokine production and release in monocytes.
  • To determine if P2Y(6) activation by UDP influences interleukin-8 (IL-8) release.
  • To explore the involvement of P2Y(6) in lipopolysaccharide-induced IL-8 production.

Main Methods:

  • Utilized human THP-1 monocytic cells and astrocytoma 1321N1 cells transfected with P2Y(6).
  • Administered UDP as a selective P2Y(6) agonist and lipopolysaccharide as a stimulus.
  • Employed P2 receptor antagonists, apyrase, and P2Y(6) antisense oligonucleotides to block receptor activity.
  • Measured IL-8 release and gene expression.

Main Results:

  • UDP specifically stimulated IL-8 release in THP-1 cells and P2Y(6)-transfected cells.
  • P2 antagonists and P2Y(6) antisense oligonucleotides inhibited UDP-induced IL-8 release.
  • Lipopolysaccharide-induced IL-8 production was inhibited by P2 antagonists and apyrase, suggesting nucleotide involvement.
  • Lipopolysaccharide-mediated IL-8 gene expression was modulated by P2Y(6) overexpression and inhibition.

Conclusions:

  • UDP activates IL-8 production in monocytic cells through the P2Y(6) receptor.
  • Lipopolysaccharide stimulates IL-8 production, at least partially, via autocrine P2Y(6) receptor activation.
  • P2Y(6) plays a novel role in the innate immune defense mechanisms of monocytes.

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