NRF2 transcriptionally regulates Caspase-11 expression to activate HMGB1 release by Autophagy-deficient hepatocytes.

ABSTRACT: Injury or stress can induce intracellular translocation and release of nuclear HMGB1, a DAMP molecule known to participate in inflammation and other pathological processes. Active release of HMGB1 from stimulated macrophages can be mediated by inflammasomes, which cleave Gasdermin D to form pores on cytoplasmic membranes. We previously had shown that active release of HMGB1 from autophagy deficient hepatocytes also depended on the inflammasome but how the inflammasome was activated was not known. Here we report that persistent activation of transcription factor NRF2 under the autophagy deficient condition led to transcriptional upregulation of Caspase-11 expression, which could then activate the CASPASE-1inflammasome. Using chromatin immunoprecipitation (CHIP) and luciferase-based reporter

SUBMITTER: Khambu B 

PROVIDER: S-EPMC10382497 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature