Feedback control of the arachidonate cascade in rheumatoid synoviocytes by 15-deoxy-Δ12,14-prostaglandin J2 Academic Article uri icon


MeSH Major

  • Arachidonic Acid
  • Arthritis, Rheumatoid
  • Feedback
  • Prostaglandin D2
  • Synovial Membrane
  • Thiazolidinediones


  • Rheumatoid arthritis (RA) is a chronic polyarticular joint disease associated with massive synovial proliferation, inflammation, and angiogenesis. PPAR-gamma ligands, both 15-deoxy-Delta(12,14)-prostaglandin J2 (15d- PGJ2) and troglitazone (TRO), can inhibit the growth of RA synoviocytes in vitro, and suppress the chronic inflammation of adjuvant-induced arthritis in rats, but the potency of 15d-PGJ2 is higher than TRO. Prostaglandin (PG) E2 plays important roles in joint erosion and synovial inflammation. In the present study, 15d-PGJ2, but not TRO and other prostanoids, suppressed interleukin (IL)-1beta-induced PGE2 synthesis in rheumatoid synovial fibroblasts (RSFs) through the inhibition of cyclooxygenase (COX-2) and cytosolic phospholipase A2 (cPLA2) expression. Furthermore, the inhibition was not affected by pretreatment with anti-PPAR-gamma antibody. It means that this anti-inflammatory effect of 15d-PGJ2 for PG synthesis may be independent of PPAR-gamma and 15d-PGJ2 is a key regulator of negative feedback of the arachidonate cascade on the COX pathway. These findings provide new insight into the feedback mechanism of the arachidonate cascade.

publication date

  • October 14, 2001



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1006/bbrc.2001.4847

PubMed ID

  • 11350047

Additional Document Info

start page

  • 750

end page

  • 5


  • 283


  • 4