The cytokine IL-1β transiently enhances P2X7 receptor expression and function in human astrocytes

Leontine Narcisse, Eliana Scemes, Yongmei Zhao, Sunhee C. Lee, Celia F. Brosnan

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

Extracellular nucleotide di- and triphosphates such as ATP and ADP mediate their effects through purinergic P2 receptors belonging to either the metabotropic P2Y or the ionotropic P2X receptor family. The P2X7R is a unique member of the P2X family, which forms a pore in response to ligand stimulation, regulating cell permeability, cytokine release, and/or apoptosis. This receptor is also unique in that its affinity for the ligand benzoyl-benzoyl ATP (BzATP) is at least 10-fold greater than that of ATP. Primary human fetal astrocytes in culture express low-levels of P2X7R mRNA and protein, and BzATP induces only a slight influx in intracellular calcium [Ca 2+]i, with little demonstrable effect on gene expression or pore formation in these cells. We now show that, following treatment with the proinflammatory cytokine IL-1β, BzATP induces a robust rise in [Ca 2+]i with agonist and antagonist profiles indicative of the P2X7R. IL-1β also induced the formation of membrane pores as evidenced by the uptake of YO-PRO-1 (375 Da). Quantitative real-time PCR demonstrated transient upregulation of P2X7R mRNA in IL-1β-treated cells, while FACS analysis indicated a similar upregulation of P2X7R protein at the cell membrane. In multiple sclerosis lesions, immunoreactivity for the P2X7R was demonstrated on reactive astrocytes in autopsy brain tissues. In turn, P2X7R stimulation increased the production of IL-1-induced nitric oxide synthase activity by astrocytes in culture. These studies suggest that signaling via the P2X 7R may modulate the astrocytic response to inflammation in the human central nervous system.

Original languageEnglish (US)
Pages (from-to)245-258
Number of pages14
JournalGLIA
Volume49
Issue number2
DOIs
StatePublished - Jan 15 2005

Fingerprint

Purinergic P2X7 Receptors
Interleukin-1
Astrocytes
Adenosine Triphosphate
Cytokines
Up-Regulation
Ligands
Purinergic P2 Receptors
Messenger RNA
Diphosphates
Nitric Oxide Synthase
Adenosine Diphosphate
Multiple Sclerosis
Real-Time Polymerase Chain Reaction
Autopsy
Permeability
Membrane Proteins
Nucleotides
Central Nervous System
Apoptosis

Keywords

  • Calcium regulation
  • Human fetal astrocytes
  • IL-1β
  • P2 receptors
  • P2XR
  • Pore formation

ASJC Scopus subject areas

  • Immunology

Cite this

Narcisse, L., Scemes, E., Zhao, Y., Lee, S. C., & Brosnan, C. F. (2005). The cytokine IL-1β transiently enhances P2X7 receptor expression and function in human astrocytes. GLIA, 49(2), 245-258. https://doi.org/10.1002/glia.20110

The cytokine IL-1β transiently enhances P2X7 receptor expression and function in human astrocytes. / Narcisse, Leontine; Scemes, Eliana; Zhao, Yongmei; Lee, Sunhee C.; Brosnan, Celia F.

In: GLIA, Vol. 49, No. 2, 15.01.2005, p. 245-258.

Research output: Contribution to journalArticle

Narcisse, L, Scemes, E, Zhao, Y, Lee, SC & Brosnan, CF 2005, 'The cytokine IL-1β transiently enhances P2X7 receptor expression and function in human astrocytes', GLIA, vol. 49, no. 2, pp. 245-258. https://doi.org/10.1002/glia.20110
Narcisse, Leontine ; Scemes, Eliana ; Zhao, Yongmei ; Lee, Sunhee C. ; Brosnan, Celia F. / The cytokine IL-1β transiently enhances P2X7 receptor expression and function in human astrocytes. In: GLIA. 2005 ; Vol. 49, No. 2. pp. 245-258.
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