PlumX Metrics
Embed PlumX Metrics

A key role for redox signaling in rapid P2X receptor-induced IL-1β processing in human monocytes

Journal of Immunology, ISSN: 1550-6606, Vol: 180, Issue: 12, Page: 8410-8420
2008
  • 101
    Citations
  • 0
    Usage
  • 76
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

P2X receptors (P2XRs) are ATP-gated ion channels that trigger caspase-1 activation in the presence of TLR ligands. Inflammatory caspase-1 is responsible for the proteolytic activation of IL-1β. However, the signaling events that couple P2XRs to caspase-1 activation remain undefined. In this study we demonstrate that ATP-induced cellular oxidation is critical for caspase-1 activation and subsequent IL-1β processing. Purinergic receptor stimulation, including P2XRs, of endotoxin-primed human monocytes augments NADPH oxidase activity whereas concurrent purinergic receptor stimulation triggers protein denitroyslation, leading to the formation of peroxynitrite. IL-1β cleavage is blocked under conditions where superoxide anion formation is blocked or monocytes are treated with antioxidants or a peroxynitrite scavenger. Nigericin, a K /H antiporter, also increases NADPH oxidase activity, leading to IL-1β and caspase-1 processing that is blocked by a peroxynitrite scavenger or inhibition of NADPH oxidase. These data demonstrate that signaling via NADPH oxidase activity is fundamental for the processing of mature IL-1β induced by P2XR stimulation. Copyright © 2008 by The American Association of Immunologists, Inc.

Bibliographic Details

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know