LPS induces fibroblast-like synoviocytes RSC-364 cells to pyroptosis through NF-κB mediated dual signalling pathway

Abstract

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.

Keywords: GSDMD; GSDME; NF-κB signal pathway; Rheumatoid arthritis (RA); pyroptosis.