TLR-induced NF-κB activation regulates NLRP3 expression in murine macrophages

Abstract

NLRP3 inflammasome plays a critical role in the activation of caspase-1 and maturation of IL-1β. However, the specific cis- and trans-regulatory elements that determine the extent of NLRP3 expression are not well defined. In this study, we found NLRP3 expression was induced by TLR agonists in murine macrophages in a NF-κB dependent manner. Furthermore, the corresponding NF-κB binding sites (nt -1303 to -1292 and -1238 to -1228) were identified in the NLRP3 promoter. Finally, EMSA and ChIP assays demonstrated LPS-induced NF-κB binding to the NLRP3 promoter. Therefore, out results delineated the molecular mechanisms involved in TLR-induced transcriptional regulation of NLRP3.