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

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.

► NLRP3 expression was induced by TLR stimulation in a NF-κB-dependent manner in murine macrophages. ► The NF-κB binding elements in NLRP3 promoter were identified. ► NF-κB binding to NLRP3 promoter was confirmed with EMSA and ChIP assays in LPS-stimulated macrophages.