15-deoxy-Δ12,14-PGJ2 induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats

被引:347
作者
Kawahito, Y
Kondo, M
Tsubouchi, Y
Hashiramoto, A
Bishop-Bailey, D
Inoue, K
Kohno, M
Yamada, R
Hla, T
Sano, H
机构
[1] Kyoto Prefectural Univ Med, Dept Internal Med 1, Kamigyo Ku, Kyoto 6028566, Japan
[2] Univ Connecticut, Ctr Hlth, Dept Physiol, Ctr Vasc Biol, Farmington, CT USA
关键词
D O I
10.1172/JCI9652
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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. Antiinflammatory 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.
引用
收藏
页码:189 / 197
页数:9
相关论文
共 59 条
[1]  
ALTOIK S, 1997, GENE DEV, V11, P1987
[2]  
[Anonymous], J CONSUMER PSYCHOL
[3]   Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans - No alteration in adipose tissue of obese and NIDDM patients [J].
Auboeuf, D ;
Rieusset, J ;
Fajas, L ;
Vallier, P ;
Frering, V ;
Riou, JP ;
Staels, P ;
Auwerx, J ;
Laville, M ;
Vidal, H .
DIABETES, 1997, 46 (08) :1319-1327
[4]   Endothelial cell apoptosis induced by the peroxisome proliferator-activated receptor (PPAR) ligand 15-deoxy-Δ12,14-prostaglandin J2 [J].
Bishop-Bailey, D ;
Hla, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (24) :17042-17048
[5]   Differential expression of peroxisome proliferator-activated receptors (PPARs): Tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat [J].
Braissant, O ;
Foufelle, F ;
Scotto, C ;
Dauca, M ;
Wahli, W .
ENDOCRINOLOGY, 1996, 137 (01) :354-366
[6]   Arachidonic acid is preferentially metabolized by cyclooxygenase-2 to prostacyclin and prostaglandin E2 [J].
Brock, TG ;
McNish, RW ;
Peters-Golden, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (17) :11660-11666
[7]   Dose-range and dose-frequency study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis [J].
Campion, GV ;
Lebsack, ME ;
Lookabaugh, J ;
Gordon, G ;
Catalano, M ;
Borenstein, D ;
Caldwell, J ;
Cohen, SA ;
Cohen, SB ;
Fleischmann, R ;
Heller, MD ;
Howard, P ;
Jaffer, AM ;
Kaine, JL ;
Kitsis, E ;
Kopp, EJ ;
Moreland, LW ;
OHanlan, M ;
Prupas, M ;
Rosenberg, A ;
Rutstein, J ;
Sack, MR ;
Schiff, MH ;
Singleton, CM ;
Taborn, J ;
Tindall, E ;
Weaver, AL ;
Yocum, D .
ARTHRITIS AND RHEUMATISM, 1996, 39 (07) :1092-1101
[8]   Activation of proliferator-activated receptors α and γ induces apoptosis of human monocyte-derived macrophages [J].
Chinetti, G ;
Griglio, S ;
Antonucci, M ;
Torra, IP ;
Delerive, P ;
Majd, Z ;
Fruchart, JC ;
Chapman, J ;
Najib, J ;
Staels, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (40) :25573-25580
[9]  
Clancy RM, 1998, ARTHRITIS RHEUM-US, V41, P1141, DOI 10.1002/1529-0131(199807)41:7<1141::AID-ART2>3.0.CO
[10]  
2-S