Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome

J Immunol. 2011 Jul 15;187(2):613-7. doi: 10.4049/jimmunol.1100613. Epub 2011 Jun 15.

Abstract

A common denominator among the multiple damage-inducing agents that ultimately lead to activation of NLRP3 has not yet been identified. Recently, production of reactive oxygen species (ROS) has been suggested to act as a common event upstream of the NLRP3 inflammasome machinery. Because de novo translation of NLRP3 is an essential step in the activation of NLRP3, we investigated the role of substances that inhibit either ROS production or its oxidative activity. Although we observe that NLRP3 inflammasome activation is unique among other known inflammasomes in its sensitivity to ROS inhibition, we have found that this phenomenon is attributable to the fact that NLRP3 strictly requires priming by a proinflammatory signal, a step that is blocked by ROS inhibitors. Although these data do not exclude a general role for ROS production in the process of NLRP3-triggered inflammation, they would put ROS upstream of NLRP3 induction, but not activation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biphenyl Compounds / pharmacology
  • Carrier Proteins / antagonists & inhibitors*
  • Carrier Proteins / physiology
  • Cells, Cultured
  • Down-Regulation / immunology*
  • Inflammasomes / antagonists & inhibitors*
  • Inflammasomes / deficiency
  • Inflammasomes / metabolism*
  • Lymphocyte Activation / immunology*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • NADPH Oxidase 2
  • NADPH Oxidases
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Onium Compounds / pharmacology
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Reactive Oxygen Species / metabolism
  • Reactive Oxygen Species / pharmacology
  • STAT1 Transcription Factor
  • Signal Transduction / immunology

Substances

  • Biphenyl Compounds
  • Carrier Proteins
  • Inflammasomes
  • Membrane Glycoproteins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Onium Compounds
  • Reactive Oxygen Species
  • STAT1 Transcription Factor
  • diphenyliodonium
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • NADPH Oxidases
  • neutrophil cytosolic factor 1