title: 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.affiliation: First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. kawahity@cam.hi-ho.ne.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Kawahito
authors.forename: M
authors.initials: M
authors.lastname: Kondo
authors.forename: Y
authors.initials: Y
authors.lastname: Tsubouchi
authors.forename: A
authors.initials: A
authors.lastname: Hashiramoto
authors.forename: D
authors.initials: D
authors.lastname: Bishop-Bailey
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Kohno
authors.forename: R
authors.initials: R
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Hla
authors.forename: H
authors.initials: H
authors.lastname: Sano
mesh_terms: D000818:Animals; D017209:Apoptosis; D001168:Arthritis / Q000188:drug therapy*; D001169:Arthritis, Experimental / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D005260:Female; D006801:Humans; D008024:Ligands; D010003:Osteoarthritis / Q000188:drug therapy; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000302:isolation & purification; D051381:Rats; D011917:Rats, Inbred Lew; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000235:genetics; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014018:Tissue Distribution; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics; D000077288:Troglitazone
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D002839:Chromans; D008024:Ligands; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone; D015230:Prostaglandin D2