1. Academic Validation
  2. Periplogenin inhibits pyroptosis of fibroblastic synoviocytes in rheumatoid arthritis through the NLRP3/Caspase-1/GSDMD signaling pathway

Periplogenin inhibits pyroptosis of fibroblastic synoviocytes in rheumatoid arthritis through the NLRP3/Caspase-1/GSDMD signaling pathway

  • Int Immunopharmacol. 2024 May 30:133:112041. doi: 10.1016/j.intimp.2024.112041.
Xi Ma 1 YuZheng Yang 1 Hao Li 2 ZeHong Luo 1 QiuYi Wang 2 XueMing Yao 2 Fang Tang 2 Ying Huang 2 Yi Ling 3 WuKai Ma 4
Affiliations

Affiliations

  • 1 Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China.
  • 2 Department of Rheumatology and Immunology, Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China.
  • 3 Department of Rheumatology and Immunology, Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China. Electronic address: lingyi794@gzy.edu.cn.
  • 4 Department of Rheumatology and Immunology, Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China. Electronic address: walker55@163.com.
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-1β, 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.

Keywords

Fibroblast-like synoviocytes; Periplogenin; Pyroptosis; Rheumatoid arthritis; Signaling pathway.

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