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Int Immunopharmacol ; 133: 112041, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38636373

ABSTRACT

Although the pathogenesis of rheumatoid arthritis (RA) remains unclear, an increasing number of studies have confirmed that pyroptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) is an important factor affecting the progression of RA. Periplogenin (PPN) is a natural cardiac glycoside; reportedly, it exerts anti-inflammatory and analgesic effects in diseases by inhibiting cell growth and migration. This study aimed to determine the effect of PPN on the growth, migration, and invasion of RA-FLS and the potential mechanism of pyroptosis regulation. We discovered that PPN could inhibit the migration and invasion abilities of RA-FLS and block their growth cycle, down-regulate the secretion and activation of NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18, and reduce the number of pyroptosis. In summary, PPN inhibited pyroptosis, reduced the release of inflammatory factors, and improved RA-FLS inflammation by regulating the NLRP3/Caspase-1/GSDMD signaling pathway.


Subject(s)
Arthritis, Rheumatoid , Fibroblasts , Pyroptosis , Signal Transduction , Synoviocytes , Humans , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , Caspase 1/metabolism , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Fibroblasts/drug effects , Gasdermins , Intracellular Signaling Peptides and Proteins/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Phosphate-Binding Proteins/metabolism , Pyroptosis/drug effects , Signal Transduction/drug effects , Synoviocytes/drug effects , Synoviocytes/metabolism , Synoviocytes/pathology
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