MPGES-1 as a novel target for arthritis

被引:73
作者
Fahmi, H [1 ]
机构
[1] Univ Montreal, Notre Dame Hosp, Ctr Hosp, Osteoarthrit Res Unit, Montreal, PQ H2L 4M1, Canada
关键词
PGE(2); mPGES-1; arthritis;
D O I
10.1097/01.bor.0000129664.81052.8e
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose of review Prostaglandin E-2, (PGE(2),) is by far the major prostanoid synthesized in the joint and plays an important role in inflammation and pathogenesis of arthritis. Moreover, increased levels of PGE(2), have been detected in serum and synovial fluids from arthritic patients. Little was known about the enzyme(s) involved in the isomerization of PGH(2), into PGE(2), synthesis until recent identification of PGE synthase (PGES). Several isoforms were characterized, among which microsomal PGES (mPGES-1) has received much attention, because this enzyme is inducible and functionally linked with cyclooxygenase-2. This review focuses on recent findings regarding the regulation of mPGES-1 expression and the possible role of this enzyme in arthritis. Recent findings Various in vitro and in vivo studies demonstrated that proinflammatory stimuli, such as interleukin-1 beta and tumor necrosis factor-alpha upregulate the expression of mPGES-1 at the protein and mRNA level. Promoter analysis indicates that the transcription factor Egr-1 is involved in the positive regulation of mPGES-1. Studies from mPGES-1 -deficient mice and animal models of inflammatory arthritis strongly suggest a role of mPGES-1 in the production of PGE(2), and the pathogenesis of arthritis. Summary This article reviews the regulation of mPGES-1 expression and provides evidence for a role of mPGES-1 in inducible PGE, production and arthritis. Future studies using selective inhibitors of mPGES-1 activity or expression would clarify the role of this enzyme in arthritis.
引用
收藏
页码:623 / 627
页数:5
相关论文
共 55 条
[1]   Superinduction of cyclooxygenase-2 activity in human osteoarthritis-affected cartilage - Influence of nitric oxide [J].
Amin, AR ;
Attur, M ;
Patel, RN ;
Thakker, GD ;
Marshall, PJ ;
Rediske, J ;
Stuchin, SA ;
Patel, IR ;
Abramson, SB .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (06) :1231-1237
[2]   IL-1β-dependent activation of NF-κB mediates PGE2 release via the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase [J].
Catley, MC ;
Chivers, JE ;
Cambridge, LM ;
Holden, N ;
Slater, DM ;
Staples, KJ ;
Bergmann, MW ;
Loser, P ;
Barnes, PJ ;
Newton, R .
FEBS LETTERS, 2003, 547 (1-3) :75-79
[3]   Microsomal prostaglandin E synthase-1 is a major terminal synthase that is selectively up-regulated during cyclooxygenase-2-dependent prostaglandin E2 production in the rat adjuvant-induced arthritis model [J].
Claveau, D ;
Sirinyan, M ;
Guay, J ;
Gordon, R ;
Chan, CC ;
Bureau, Y ;
Riendeau, D ;
Mancini, JA .
JOURNAL OF IMMUNOLOGY, 2003, 170 (09) :4738-4744
[4]  
Cohen EG, 2003, CLIN CANCER RES, V9, P3425
[5]  
Crosby Colin G, 2003, Expert Opin Emerg Drugs, V8, P1
[6]   Lipopolysaccharide-induced increase of prostaglandin E2 is mediated by inducible nitric oxide synthase activation of the constitutive cyclooxygenase and induction of membrane-associated prostaglandin E synthase [J].
Devaux, Y ;
Seguin, C ;
Grosjean, S ;
de Talancé, N ;
Camaeti, V ;
Burlet, A ;
Zannad, F ;
Meistelman, C ;
Mertes, PM ;
Longrois, D .
JOURNAL OF IMMUNOLOGY, 2001, 167 (07) :3962-3971
[7]   Inflammatory response - Pathway across the blood-brain barrier [J].
Ek, M ;
Engblom, D ;
Saha, S ;
Blomqvist, A ;
Jakobsson, PJ ;
Ericsson-Dahlstrand, A .
NATURE, 2001, 410 (6827) :430-431
[8]   Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis [J].
Engblom, D ;
Saha, S ;
Engström, L ;
Westman, M ;
Audoly, LP ;
Jakobsson, PJ ;
Blomqvist, A .
NATURE NEUROSCIENCE, 2003, 6 (11) :1137-1138
[9]  
Fahmi H, 2002, J RHEUMATOL, V29, P3
[10]   Human glutathione dependent prostaglandin E synthase:: gene structure and regulation [J].
Forsberg, L ;
Leeb, L ;
Thorén, S ;
Morgenstern, R ;
Jakobsson, PJ .
FEBS LETTERS, 2000, 471 (01) :78-82