FEBS Letters · 2012 · 338 citations · 6 references
Life SciencesImmunologyMolecular BiologyCell SignalingInnate ImmunitySignal TransductionInflammasome ActivationInflammatory Response RegulationInflammatory SignalingInnate Immune Signaling PathwaysMacrophage BiologyNod-like ReceptorsInflammasome SignalingMacrophage Inflammasome ActivationMacrophage Signaling PathwaysMacrophage Toll-like Receptor SignalingNlr Family Pyrin Domain-containing 3 InflammasomeNlrp3 InflammasomeTrans-acting Regulatory ElementsUpstream Regulatory Elements
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.
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