High glucose reduces Nrf2-dependent cRAGE release and enhances inflammasome-dependent IL-1β production in monocytes: the modulatory effects of EGCG

Soluble receptor for advanced glycation end products (sRAGE) acts as a decoy sequestering of RAGE ligands, thus preventing the activation ligand-RAGE axis linking human diseases. However, molecular mechanisms underlying sRAGE remain unclear. In this study, THP-1 monocytes were cultured in normal glucose (NG, 5.5 mmol/L) and high (HG, 15 to investigate effects diabetes-relevant concentrations on IL-1β secretion. The modulatory epigallocatechin gallate (EGCG) response HG challenge also evaluated. enhanced intracellular reactive oxygen species (ROS) generation expression. secretion sRAGE, including esRAGE cRAGE, was reduced under conditions, together with downregulation ADAM10 Nrf2 nuclear translocation. Mechanistically, counteracted by siRAGE exacerbated siNrf2. Chromatin immunoprecipitation results showed that binding promoter interfered binding. Our data reinforce notion might be sRAGE-regulating factors. Under treatment EGCG ROS activation. EGCG-stimulated cRAGE release likely caused upregulation Nrf2-ADAM10 pathway. inhibited HG-mediated NLRP3 inflammasome at least partly stimulating thereby reducing release.