Feedback control of the arachidonate cascade in rheumatoid synoviocytes by 15-deoxy-Delta(12,14)-prostaglandin J2

Biochem Biophys Res Commun. 2001 May 18;283(4):750-5. doi: 10.1006/bbrc.2001.4847.

Abstract

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.

MeSH terms

  • Arachidonic Acid / metabolism*
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • Chromans / pharmacology
  • Cyclooxygenase 2
  • Cysteine / antagonists & inhibitors
  • Cysteine / biosynthesis
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / biosynthesis
  • Feedback*
  • Humans
  • Isoenzymes / immunology
  • Isoenzymes / metabolism
  • Leukotriene Antagonists
  • Leukotriene B4 / antagonists & inhibitors
  • Leukotriene B4 / biosynthesis
  • Leukotrienes / biosynthesis
  • Membrane Proteins
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / metabolism*
  • Prostaglandin-Endoperoxide Synthases / immunology
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Receptors, Cytoplasmic and Nuclear / immunology
  • Synovial Membrane / metabolism*
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / immunology
  • Troglitazone

Substances

  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Chromans
  • Isoenzymes
  • Leukotriene Antagonists
  • Leukotrienes
  • Membrane Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • cysteinyl-leukotriene
  • Leukotriene B4
  • Arachidonic Acid
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Troglitazone
  • Dinoprostone
  • Cysteine
  • Prostaglandin D2