Journal of agricultural and food chemistry [J Agric Food Chem] 2025 Apr 16; Vol. 73 (15), pp. 9382-9397. Date of Electronic Publication: 2025 Apr 06.

Publisher: American Chemical Society Country of Publication: United States NLM ID: 0374755 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5118 (Electronic) Linking ISSN: 00218561 NLM ISO Abbreviation: J Agric Food Chem Subsets: MEDLINE

HMGB1 Protein*/genetics , HMGB1 Protein*/immunology , HMGB1 Protein*/metabolism , Extracellular Traps*/genetics , Extracellular Traps*/immunology , Extracellular Traps*/metabolism , Reactive Oxygen Species*/immunology , Reactive Oxygen Species*/metabolism , Selenoproteins*/genetics , Selenoproteins*/immunology , Selenoproteins*/metabolism, Animals ; Mice ; Mice, Knockout ; Mice, Inbred C57BL ; Male ; Liver/immunology ; Liver/metabolism ; Neutrophils/immunology ; Humans

Selenoproteins (Sels) are a class of essential biomolecules that play critical roles in cellular homeostasis. SelO was identified as the preferential source of selenium in the liver, implying its potential as a key regulatory factor in hepatic pathophysiology. Bioinformatics analysis of data from GEO data sets revealed marked downregulation of SelO in liver injury. However, its function and regulatory mechanisms in the liver remain unclear. To address this, we investigated the effect of SelO ablation on acute liver inflammation, focusing on its association with inflammation and neutrophil extracellular traps (NETs) formation. Wild-type (WT) and SelO -knockout mice were used to establish a lipopolysaccharide (LPS) exposure model and a coculture model (AML12 cells and neutrophils) in vitro. Our findings revealed that LPS stimulation significantly reduced SelO expression in the WT mouse liver. SelO deletion promoted the expression of Hmgb1 and marker cytokines for chemokines, NETs generation, pyroptosis and inflammation, and induced an imbalance in redox homeostasis. Immunofluorescence, SYTOX staining, and scanning electron microscopy confirmed that SelO silencing promoted reactive oxygen species (ROS)-dependent NETs formation. Moreover, the coculture model demonstrated that excessive NETs formation exacerbated SelO -ablation-induced hepatic inflammation. Importantly, we confirmed the significant involvement of the Hmgb1/ROS axis in the development of acute liver inflammation in the absence of SelO . Our results demonstrated that SelO ablation promoted neutrophil recruitment and enhanced ROS-dependent NETs formation by increasing Hmgb1 expression levels, thereby aggravating LPS-induced pyroptosis and inflammation. This study not only uncovered the crucial biological functions of SelO , but also shed light on its regulatory implications in the inflammatory process.