Rheumatoid arthritis (RA) is a chronic, progressive, and systemic inflammatory joint disease characterized by synovial inflammation and joint damage. Abnormal activation of fibroblast-like synoviocytes is an initial event of synovial inflammation and joint damage, which can significantly aggravate the progression of RA. Clinical studies have shown that synovitis may be associated with pyroptosis. Therefore, this study is mainly aim for exploring the underlying mechanisms of relationship between inflammation and pyroptosis during synovitis. A cell model of synovitis was constructed by stimulating synovial fibroblasts RSC-364 cells with lipopolysaccharide (LPS). In vitro, we found that LPS can induce pyroptosis of synovial fibroblasts through NOD-like receptor pyrin domain-3/caspase-1/gasdermin D and caspase-3/gasdermin E two signaling pathways, and these two signaling pathways can promote each other. In addition, NF-κB signaling pathway, as the upstream of these two pathways, is involved in regulating the pyroptosis of synovial fibroblast. These results suggest that pyroptosis may be triggered during the occurrence of RA. We hope to provide a new perspective for the study of RA and a new therapeutic target for clinical treatment of RA.

类风湿关节炎（RA）是一种以滑膜炎症和关节损伤为特征的慢性、进行性和全身性炎症性关节疾病。成纤维细胞样滑膜细胞的异常激活是滑膜炎症和关节损伤的初始事件，可显着加重类风湿关节炎的进展。临床研究表明，滑膜炎可能与细胞焦亡有关。因此，本研究主要旨在探索滑膜炎炎症与细胞焦亡关系的潜在机制。通过用脂多糖（LPS）刺激滑膜成纤维细胞RSC-364细胞构建滑膜炎细胞模型。在体外，我们发现LPS可以通过NOD样受体pyrin domain-3/caspase-1/gasdermin D和caspase-3/gasdermin E两个信号通路诱导滑膜成纤维细胞焦亡，而这两条信号通路可以相互促进。此外，NF-κB信号通路作为这两条通路的上游，参与调节滑膜成纤维细胞的焦亡。这些结果表明在 RA 发生期间可能会触发细胞焦亡。我们希望为类风湿关节炎的研究提供一个新的视角，为类风湿关节炎的临床治疗提供一个新的治疗靶点。