DBDPE upregulates NOD-like receptor signaling to induce NLRP3 inflammasome-mediated HAECs pyroptosis

Decabromodiphenyl ethane (DBDPE), a typical new brominated flame retardant (BFR), is a widespread new pollutant in the environment. Several studies and our previous studies have found that DBDPE can cause aortic endothelial injury and aortic endothelial cell pyroptosis, whereas the molecular mechanism involved has not been elucidated. In this study, we exposed human aortic endothelial cells (HAECs) to 25 μmol/L of DBDPE and analyzed the gene expression profiles by Affymetrix PrimeView™ Human Gene Expression Chip. The results showed that 886 genes were differentially expressed in the DBDPE exposure group. Enrichment analyses revealed that differentially expressed genes were mainly enriched in the inflammatory response and NOD-like receptor signal pathway. Gene-gene functional interaction analyses and crossover genes and pathways analyses found that the NOD-like receptor signal pathway may be involved in regulating NLRP3 and IL-18. We found that NOD2 cannot interact with NLRP3 directly through an immunoprecipitation experiment. Thus, we construct the RIPK2 knockdown HAECs cell line to repress the NOD-like receptor signaling and further study the mechanism of DBDPE-activated NLRP3 inflammasome to induce HAECs pyroptosis. The results showed that RIPK2 knockdown could repress DBDPE-induced NOD-like receptor signaling pathway upregulation, inhibit NLRP3 inflammasome activation, and decrease HAECs pyroptosis. In addition, RIPK2 knockdown decreased the ROS generation in HAECs induced by DBDPE. And NAC pretreated HAECs inhibited DBDPE-induced NLRP3 inflammasome activation and HAECs pyroptosis. These results demonstrated that DBDPE upregulated NOD-like receptor signaling to induce ROS generation and, in turn, activated NLRP3 inflammasome, leading to HAECs pyroptosis. [Display omitted] •DBDPE activated NLRP3 inflammasome to lead HAECs pyroptosis.•DBDPE-induced DEGs were enriched in the NOD-like receptor signaling pathway.•DBDPE upregulated NOD2/RIPK2/XIAP/NF-κΒ signaling pathway.•DBDPE activated NLRP3 inflammasome by upregulating NOD-like receptor signaling.