MO018QUORUM SENSING MOLECULE INDUCES THE RECEPTOR-INTERACTING PROTEIN KINASE 1-DEPENDENT APOPTOSIS SYNERGISTICALLY WITH LIPOPOLYSACCHARIDE IN ENDOTHELIAL CELLS

Abstract

Abstract Background and Aims Endothelial dysfunction is an initial step for sepsis-associated organ failure. Bacterial quorum sensing molecules play as pathogen-associated molecular patterns, however, the impact of quorum sensing molecules on endothelial cells remains uncertain. This study investigated the molecular mechanism of quorum sensing molecule-induced cell death and the interaction with lipopolysaccharide (LPS) in human umbilical vein endothelial cells. Method Endothelial cells were treated with varying concentrations of N-3-oxododecanoyl-HSL (3OC12-HSL) and LPS derived from Pseudomonas aeruginosa. Results Treatment of 3OC12-HSL reduced cell viability in dose-dependent manners, and the combination of this molecule and LPS exacerbated cell deaths in compared to single treatment of LPS. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay revealed that there were clear increases in apoptotic death following the 3OC12-HSL treatment. Treatment of 3CO12-HSL activated the receptor-interacting protein kinase 1 (RIPK1) pathway, resulting in increases in expression of caspase 8 and caspase 3. Moreover, the combination treatment of LPS and 3OC12-HSL amplified these expressions. Conclusion Treatment of 3OC12-HSL reduces endothelial cell viability, and this effect is synergistical with LPS. 3OC12-HSL induces apoptotic cell death, through the activation of the RIPK1 pathway, moreover, it is amplified in combination with LPS.