Immunodynamic axis of fibroblast-driven neutrophil infiltration in acute pancreatitis: NF-κB–HIF-1α–CXCL1

作者：Qiang Wang, Xiao Zhang, Chenglong Han, Zhenyi Lv, Yi Zheng, Xuxu Liu, Zhiwei Du, Tianming Liu, Dongbo Xue, Tao Li, Liyi Wang · 发表于：Cellular & Molecular Biology Letters · 年份：2025 · DOI：10.1186/s11658-025-00734-6 · 被引用次数：23 · 研究领域：Pancreatitis Pathology and Treatment、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Pancreatic and Hepatic Oncology Research

BACKGROUND: Acute pancreatitis (AP) is a sterile inflammation, and 10-20% of cases can progress to severe acute pancreatitis (SAP), which seriously threatens human life and health. Neutrophils and their extracellular traps (NETs) play an important role in the progression of AP. However, the immunodynamic factors between the excessive infiltration of neutrophils during the occurrence of AP have not been fully elucidated. METHODS: , NAC, and JSH-2, and co-cultured with neutrophils in Transwell chambers. The severity of inflammation was evaluated, and the molecular mechanism by which fibroblasts exacerbate AP was revealed through techniques such as cell colony formation assay, cell migration assay, cell transfection, immunofluorescence, flow cytometry, Western blot, reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and co-immunoprecipitation (co-IP). RESULTS: The study showed that the elimination of neutrophils and NETs could significantly improve AP. Single-cell RNA sequencing (scRNA-seq) indicated that both neutrophils and fibroblasts in pancreatic tissue exhibited heterogeneity during AP. Among them, neutrophils highly expressed CXCR2, and fibroblasts highly expressed CXCL1. Further experimental results demonstrated that the infiltration of neutrophils in the early stage of AP was related to the activation of fibroblasts. The activation of fibroblasts depended on the nuclear factor kappa B (NF-κB) signaling pathway induced by hypoxia. NF-κB enhanced the ...