Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 43, Issue 5, Pages 1147-1152Publisher
WILEY
DOI: 10.1002/eji.201243187
Keywords
Caspase-1; IL-1; Inflammasome; Macrophages; PKR
Categories
Funding
- National Institutes of Health [R01AI063331, R01DK091191]
- Crohn's and Colitis Foundation of America
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Inflammasomes are multi-protein platforms that drive the activation of caspase-1 leading to the processing and secretion of biologically active IL-1 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-1/IL-18 and secretion of IL-1 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.
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