Role of soluble epoxide hydrolase in the abnormal activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis

Clin Immunol. 2023 Dec:257:109850. doi: 10.1016/j.clim.2023.109850. Epub 2023 Nov 25.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by enigmatic pathogenesis. Polyunsaturated fatty acids (PUFAs) are implicated in RA's development and progression, yet their exact mechanisms of influence are not fully understood. Soluble epoxide hydrolase (sEH) is an enzyme that metabolizes anti-inflammatory epoxy fatty acids (EpFAs), derivatives of PUFAs. In this study, we report elevated sEH expression in the joints of CIA (collagen-induced arthritis) rats, concomitant with diminished levels of two significant EpFAs. Additionally, increased sEH expression was detected in both the synovium of CIA rats and in the synovium and fibroblast-like synoviocytes (FLS) of RA patients. The sEH inhibitor TPPU attenuated the migration and invasion capabilities of FLS derived from RA patients and to reduce the secretion of inflammatory factors by these cells. Our findings indicate a pivotal role for sEH in RA pathogenesis and suggest that sEH inhibitors offer a promising new therapeutic strategy for managing RA.

Keywords: Fibroblast-like synoviocytes; Inflammation; Rheumatoid arthritis; Soluble epoxide hydrolase; Synovium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid* / enzymology
  • Arthritis, Rheumatoid* / pathology
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Epoxide Hydrolases / metabolism
  • Fibroblasts / metabolism
  • Humans
  • Rats
  • Synovial Membrane / metabolism
  • Synoviocytes* / metabolism

Substances

  • Epoxide Hydrolases
  • EPHX2 protein, rat
  • EPHX2 protein, human