Glycyrrhizin inhibits LPS-induced neutrophil-like release of NETs
Zixuan Shen1, Jiarun Gu2, Baowei Jiang2
1Department of Emergency Surgery, The Affiliated Hospital of Guizhou Medical University Guiyang 550001, Guizhou, China.
Objective:
To investigate the regulatory effect of glycyrrhizin (GL) on the release of neutrophil extracellular traps (NETs) from neutrophils in sepsis.
Methods:
HL-60 cells were induced to differentiate into neutrophil-like dHL-60 cells to establish a neutrophil-like sepsis model. Expression levels of high-mobility group box 1 (HMGB1), citrullinated histone H3 (Cit-H3), and Toll-like receptor 9 (TLR9) were assessed by Western blotting. Free DNA, a component of NETs, was quantified using a fluorescence microplate reader. Cellular immunofluorescence analysis was used to detect the expression of the key NETs protein, Cit-H3.
Results:
dHL-60 cells stimulated with 200 ng/ml LPS exhibited the highest expression of Cit-H3. The neutrophil-like sepsis model showed significantly increased levels of Cit-H3 and HMGB1. GL intervention significantly reduced the expression levels of HMGB1 and Cit-H3 and decreased the free DNA level. These findings suggest that GL decreases HMGB1 expression and NET release in the neutrophil-like sepsis model. TLR9 expression was significantly elevated in the sepsis model. Exogenous recombinant human HMGB1 protein further increased TLR9 expression, while GL inhibited this increase.
Conclusion:
GL may inhibit NET release in sepsis through the HMGB1/TLR9 pathway.
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