The protein kinase PKR is critical for LPS-induced iNOS production but dispensable for inflammasome activation in macrophages

Eur J Immunol. 2013 May;43(5):1147-52. doi: 10.1002/eji.201243187. Epub 2013 Mar 15.

Abstract

Inflammasomes are multi-protein platforms that drive the activation of caspase-1 leading to the processing and secretion of biologically active IL-1β and IL-18. Different inflammasomes including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLR caspase-recruitment domain-containing 4 (NLRC4) and absent in melanoma 2 (AIM2) are activated and assembled in response to distinct microbial or endogenous stimuli. However, the mechanisms by which upstream stimuli trigger inflammasome activation remain poorly understood. Double-stranded RNA-activated protein kinase (PKR), a protein kinase activated by viral infection, has been recently shown to be required for the activation of the inflammasomes. Using macrophages from two different mouse strains deficient in PKR, we found that PKR is important for the induction of the inducible nitric oxide synthase (iNOS). However, PKR was dispensable for caspase-1 activation, processing of pro-IL-1β/IL-18 and secretion of IL-1β induced by stimuli that trigger the activation of NLRP3, NLRC4 and AIM2. These results indicate that PKR is not required for inflammasome activation in macrophages.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / immunology
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / immunology
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology
  • Caspase 1 / genetics
  • Caspase 1 / immunology
  • Cells, Cultured
  • DNA-Binding Proteins
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Inflammasomes / genetics
  • Inflammasomes / immunology
  • Interleukin-18 / immunology
  • Interleukin-18 / metabolism
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Mice, Knockout
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nitric Oxide Synthase Type II / biosynthesis
  • Nitric Oxide Synthase Type II / immunology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology
  • Protein Precursors / immunology
  • Protein Precursors / metabolism
  • eIF-2 Kinase / deficiency
  • eIF-2 Kinase / genetics
  • eIF-2 Kinase / immunology*

Substances

  • Aim2 protein, mouse
  • Apoptosis Regulatory Proteins
  • Calcium-Binding Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • Ipaf protein, mouse
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Nuclear Proteins
  • Protein Precursors
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • eIF-2 Kinase
  • Caspase 1