NLRP3 in myocardial ischaemia-reperfusion injury: inflammasome-dependent or -independent role in different cell types

Abstract

This editorial refers to ‘The NLRP3 inflammasome is up-regulated in cardiac fibroblasts and mediates myocardial ischaemia–reperfusion injury’ by O. Sandanger et al. , pp. 164–174, this issue. An accumulating body of evidence has indicated that inflammation in the absence of pathogens, which is referred to as sterile inflammation, is mediated through an inflammasome, a large multiple protein complex in the cytosol that induces caspase-1 activation. Till date, several types of the inflammasomes have been documented. The best-characterized inflammasome is the nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3; also known as NALP3 and cryopyrin) inflammasome, which is known to participate in the pathophysiology of sterile inflammation.1 The NLRP3 inflammasome contains NLRP3 that interact with the adaptor molecule an apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC; also known as Pycard), which recruits and activates caspase-1. Because caspase-1 is an interleukin (IL)-1β-converting enzyme (ICE), it induces the processing of pro-IL-1β into mature IL-1β and the release of IL-1β, thereby causing inflammation and tissue damage. However, the induction of IL-1β release requires another signal provided by the transcriptional induction of pro-IL-1β. Hence, a system comprising pro-IL-1β induction and inflammasome-mediated IL-1β processing is believed to be necessary for the tight regulation of this potent inflammatory …