Critical role for post-transcriptional regulation of the gene encoding the key inflammasome protein NLRP3

Abstract

The NLRP3 inflammasome regulates the maturation of the pro-inflammatory cytokines IL-1β and IL-18, which are important mediators in inflammatory disorders such as atherosclerosis, Type 2 diabetes and Alzheimer’s disease. Given its role as an inflammatory gatekeeper, NLRP3 expression is tightly controlled. It is transcriptionally regulated by NF-κB as well as post-translationally by S-nitrosylation and ubiquitination.We decided to test whether NLRP3 is also regulated at the post-transcriptional level. We found that the NLRP3 3’ untranslated region (UTR) contains an evolutionarily conserved target site for miRNA-223 and we confirmed miR-223 as a direct negative regulator of NLRP3 using a lucif..