Temporal interleukin-1beta secretion from primary human peripheral blood monocytes by P2X7-independent and P2X7-dependent mechanisms

Jon R Ward, Peter W West, Mark P Ariaans, Lisa C Parker, Sheila E Francis, David C Crossman, Ian Sabroe, Heather L Wilson

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The processing and regulated secretion of IL-1beta are critical points of control of the biological activity of this important pro-inflammatory cytokine. IL-1beta is produced by both monocytes and macrophages, but the rate and mechanism of release differ according to the differentiation status and the origin of these cells. We aimed to study the control of processing and release in human blood monocytes and human monocyte-derived macrophages. Toll-like receptor (TLR)-induced IL-1beta production and release were investigated for dependence upon caspase-1, P2X7 receptor activation, and loss of membrane asymmetry associated with microvesicle shedding. TLR agonists induced P2X7 receptor-dependent IL-1beta release in both monocytes and macrophages; however, only monocytes also showed P2X7 receptor-independent release of mature IL-1beta. Furthermore, in monocytes ATP-mediated PS exposure could be activated independently of IL-1beta production. Release of IL-1beta from monocytes showed selectivity for specific TLR agonists and was accelerated by P2X7 receptor activation. Human monocytes released more IL-1beta/cell than macrophages. These data have important implications for inflammatory diseases that involve monocyte activation and IL-1 release.
Original languageEnglish
Pages (from-to)23147-23158
Number of pages12
JournalJournal of Biological Chemistry
Volume285
Issue number30
DOIs
Publication statusPublished - 23 Jul 2010

Keywords

  • Adenosine Triphosphate
  • Caspase 1
  • Cell Line, Tumor
  • Enzyme Activation
  • Humans
  • Interleukin-1beta
  • Macrophages
  • Monocytes
  • Phosphatidylserines
  • Quinolines
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7
  • Time Factors
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8

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