15-deoxy-delta(12,14)-PGJ(2) induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats.

Abstract

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily and have a dominant regulatory role in adipocyte and monocyte differentiation. PPAR-gamma agonists are also negative regulators of macrophage activation and have modulatory effects on tumorigenesis. In this study we demonstrate that synovial tissue localized expression of PPAR-gamma in patients with rheumatoid arthritis (RA). We detected markedly enhanced expression of PPAR-gamma in macrophages, as well as modestly enhanced expression in the synovial lining layer, fibroblasts, and endothelial cells. Activation of the PPAR-gamma by 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and the synthetic PPAR-gamma ligand (troglitazone) induced RA synoviocyte apoptosis in vitro. Moreover, intraperitoneal administration of these PPAR-gamma ligands ameliorated adjuvant-induced arthritis with suppression of pannus formation and mononuclear cell infiltration in female Lewis rats. Anti-inflammatory effects of 15d-PGJ(2) were more potent than troglitazone. These findings suggest that PPAR-gamma may be an important immunoinflammatory mediator and its ligands, especially 15d-PGJ(2), may be useful in the treatment of RA.

• Authors: Y Kawahito, M Kondo, Y Tsubouchi, A Hashiramoto, D Bishop-Bailey, K Inoue, M Kohno, R Yamada, T Hla, H Sano
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 106 Issue 2 Pg. 189-97 (Jul 2000) ISSN: 0021-9738 [Print] United States
• PMID: 10903334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 15-deoxy-delta(12,14)-prostaglandin J2
• Chromans
• Ligands
• RNA, Messenger
• Receptors, Cytoplasmic and Nuclear
• Thiazoles
• Thiazolidinediones
• Transcription Factors
• Troglitazone
• Prostaglandin D2

Topics

• Animals
• Apoptosis
• Arthritis (drug therapy)
• Arthritis, Experimental (drug therapy)
• Arthritis, Rheumatoid (drug therapy)
• Cells, Cultured
• Chromans (pharmacology)
• Female
• Humans
• Ligands
• Osteoarthritis (drug therapy)
• Prostaglandin D2 (analogs & derivatives, pharmacology, therapeutic use)
• RNA, Messenger (isolation & purification)
• Rats
• Rats, Inbred Lew
• Receptors, Cytoplasmic and Nuclear (drug effects, genetics)
• Synovial Membrane (cytology, drug effects)
• Thiazoles (pharmacology)
• Thiazolidinediones
• Tissue Distribution
• Transcription Factors (drug effects, genetics)
• Troglitazone