Work

Neutrophil extracellular traps induce hepatocyte pyroptosis via CCDC25 in sepsis-associated liver injury

Year: 2025

Type: article

Abstract: = 0.6727/0.8884) and predict higher 90-day mortality. Critically, we identify a novel NETs-CCDC25-pyroptosis axis driving SALI pathogenesis: Lipopolysaccharide (LPS)-activated NETs upregulate the hepatocyte transmembrane receptor CCDC25, which synchronizes with liver injury severity and directly triggers hepatocyte pyroptosis and inflammatory cytokine release. This cascade is reversed by NETs disruption (DNase I or Cl-amidine) or CCDC25 silencing in vitro. Therapeutically, inhibiting NETs with Cl-amidine or knocking down CCDC25 with si-CCDC25 in vivo reduces liver enzymes, suppresses pyroptosis executors (e.g., GSDMD-N), and attenuates histopathological damage. This study clarifies the mechanism of the NETs-CCDC25-pyroptosis axis in SALI, offering a novel targeted therapeutic strategy for clinical practice.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2025.115991

Authors: Zhiyu Li, Yumeng Xiao, Lan Yang, Fengming Liang, Hongyang Xu, Fei Gao

Institutions: Wuxi People's Hospital, Nanjing Medical University

Language: English

Topic: Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,220