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J Clin Invest. 2000 Jul;106(2):189-97.

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

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1
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. kawahity@cam.hi-ho.ne.jp

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.

PMID:
10903334
PMCID:
PMC314310
DOI:
10.1172/JCI9652
[Indexed for MEDLINE]
Free PMC Article
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