Sirt1 inhibits macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK/NF-κB/AP-1 pathway and activating the Nrf2/HO-1 pathway

• DOI: 10.1007/s00011-024-01890-9
• Publication Date: 2024-05-13T13:03:07Z
• Authors: Xu Zhao; Menglan Li; Yiwei Lu; Mi Wang; Jiawei Xiao; Qingqing Xie; Xinyi He; Shiquan Shuai
• Keywords: CD68; Macrophage polarization; Inflammatory arthritis

Abstract Objective and design To elucidate Sirt1’s role in gouty arthritis inflammation its potential mechanisms. Material Constructed murine models of conducted THP-1 cell experiments. Treatment 1 mg MSU crystals injected into mice ankle joints for a 72-h intervention. After 3-h pre-treatment with Sirt1-specific inhibitor (EX527) agonist (SRT2104), was induced 21 h using lipopolysaccharide (LPS) plus crystals. Methods We assessed severity through joint index, swelling, hematoxylin eosin (H&E) staining, measured CD68 mononuclear macrophages Sirt1 expression synovial tissue via immunohistochemistry. ELISA, NO assay, RT-qPCR, Flow cytometry, Western blot were utilized to examine macrophage inflammatory factors, polarization, reactive oxygen species(ROS), MAPK/NF-κB/AP-1 Nrf2/HO-1 pathways proteins. Results Significant edema, infiltration observed. elevated synovium. activation decreased M1 ROS generation. reduced p38/JNK phosphorylation, thereby inhibiting downstream NF-κB p65/AP-1 enhancing Nrf2/HO-1, thus suppressing inflammation. Conclusions alleviates polarization by the pathway activating pathway. Thus, may provide new therapeutic target arthritis.