AB0077 High-mobility group box 1 mediated monosodium urate crystal-induced nlrp3 inflammasome activation in human macrophages. (12th June 2018) - Kim, S.-K.
Abstract : Background: High-mobility group box 1 (HMGB1) was identified originally as a highly conserved non-histone DNA-binding factor and recently noted as a potent inflammatory mediator under inflammatory conditions. Objectives: This study is to investigate the inflammatory cascade between HMGB1 protein and activation of NLRP3 inflammasome in human macrophage under uric acid-induced inflammation. Methods: The study used human U937 macrophage cell line under stimulation with monosodium urate (MSU) crystal or HMGB1. Total reactive oxygen species (ROS) were measured by flow cytometry. Interleukin-1b (IL-1b), NLRP3, TXNIP, HMGB1, NF-kB, IkBa, and caspase-1 protein expression was detected using western blotting. IL-1b, IL-18, caspase-1, and HMGB1 gene expression were assessed by quantitative real-time polymerase chain reaction. Intracellular HMGB1 expression was assessed by immunofluorescent staining with MitoTracker Red. Results: MSU crystals induced HMGB1 and ROS production by activation of NF-kB signal pathway in human macrophages. HMGB1 mRNA expression was markedly attenuated under stimulation using TXNIP siRNA. Enhanced release of IL-1 was noted through increased HMGB1 expression and TXNIP-mediated NLRP3 infammasome activation under stimulation of MSU. Combination of MSU and HMGB1 augmented NLRP3 inflammasome, compared to either MSU or HMGB1 stimulation. Conclusions: This study demonstrated that HMGB1 is a crucial molecule for ROS-mediated TXNIP and NLRP3 inflammasome activation in uric acid-induced inflammation. Disclosure of Interest: None declared