Journal
IMMUNOBIOLOGY
Volume 217, Issue 12, Pages 1325-1329Publisher
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.imbio.2012.07.020
Keywords
Inflammasome; Lipopolysaccharide; Priming; Caspase-1
Categories
Funding
- Australian National Health and Medical Research Council (NHMRC) [1023297, 631472, 631531]
- NHMRC [490993]
- Australian Research Council (ARC) [FT0991576]
- ARC Future Fellowship [FT100100657]
- Honorary Australian NHMRC Senior Research Fellowship [1003470]
- Australian Research Council [FT0991576] Funding Source: Australian Research Council
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Macrophage pre-treatment with bacterial lipopolysaccharide (LPS) boosts subsequent activation of the NLRP3 inflammasome, which controls caspase-1-dependent pro-inflammatory cytokine maturation. Previous work has attributed this phenomenon (known as LPS 'priming') to LPS-dependent induction of NLRP3 expression. Whilst this plays a role, here we demonstrate that rapid LPS priming of NLRP3 inflammasome activation can occur independently of NLRP3 induction, since the priming effect of LPS is still apparent at short pre-treatment times in which NLRP3 protein expression remains unchanged. Furthermore, rapid LPS priming is still evident in Nlrp3(-/-) primary macrophages with NLRP3 expression reconstituted using a constitutive promoter. Similarly, we found that LPS potentiates AIM2 inflammasome activation to submaximal doses of cytosolic DNA without concomitant upregulation of AIM2 protein expression. Our data suggest that, in addition to augmenting NLRP3 inflammasome activity via NLRP3 induction, LPS boosts caspase-1 activation by the NLRP3 and AIM2 inflammasomes by an acute mechanism that is independent of inflammasome sensor induction. (C) 2012 Elsevier GmbH. All rights reserved.
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