The role and impact of the IL-6 mediated JAK2-STAT1/3 signaling pathway in the pathogenesis of gout

作者：Zeng Zhang, Peng Wang, Tianyi Lei, Jianwei Guo, Yiguo Jiang, Yanhui Li, Jianxiong Zheng, Shunbing Wang, Haimuzi Xu, Guilin Jian, Quan‐Bo Zhang, Yufeng Qing · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1480844 · 被引用次数：10 · 研究领域：Gout, Hyperuricemia, Uric Acid、Cytokine Signaling Pathways and Interactions、Inflammasome and immune disorders

Background: Interleukin-6 (IL-6) is a pleiotropic cytokine, with specific effects depending on the immune microenvironment. Extensive research has confirmed the pathological roles of the IL-6/JAK2/STAT1/3 signaling pathway in inflammation, autoimmunity, and cancer, as well as its involvement in the pathogenesis of various rheumatic diseases. However, the role and impact of IL-6 as an upstream regulator of the JAK2-STAT1/3 pathway in gout have seldom been reported. This study explores the influence and role of upstream IL-6 in regulating the JAK2-STAT1/3 signaling pathway on gout inflammation, offering new insights for targeted therapeutic interventions and drug development in gout management. Methods and Results: Clinical data and peripheral blood specimens were collected from gout patients and healthy individuals. In vitro and in vivo models of acute gout inflammation were established by stimulating PBMCs, THP-1 cells, and mice with MSU crystals. IL-6 expression was manipulated using IL-6 agonists and IL-6 knockout (KO) mouse technology to investigate the role and impact of the IL-6-mediated JAK2-STAT1/3 signaling pathway in gout models. RT-qPCR, WB, and ELISA were utilized to assess gene and protein expression levels. Paw swelling in mice was measured using a caliper gauge, while HE and IHC staining were conducted to evaluate the inflammatory status of mouse paw pad synovial tissues and detect the positive expression of relevant proteins. Serum IL-6 protein expression level...