Peroxisome proliferator-activated receptor gamma agonists as therapy for chronic airway inflammation

被引:111
作者
Belvisi, MG [1 ]
Hele, DJ [1 ]
Birrell, MA [1 ]
机构
[1] Natl Heart & Lung Inst, Fac Med, Imperial Coll, London SW3 6LY, England
关键词
PPAR gamma; airway; inflammation; asthma;
D O I
10.1016/j.ejphar.2005.12.048
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPAR gamma regulates several metabolic pathways by binding to sequence-specific PPAR response elements in the promoter region of target genes, including lipid biosynthesis and glucose metabolism. Synthetic PPAR gamma agonists have been developed, such as the thiazolidinediones rosiglitazone and pioglitazone. These act as insulin sensitizers and are used in the treatment of type 2 diabetes. Recently however, PPAR gamma ligands have been implicated as regulators Of cellular inflammatory and immune responses. They are thought to exert anti-inflammatory effects by negatively regulating the expression of pro-inflammatory genes. Several Studies have demonstrated that PPAR gamma ligands possess anti-inflammatory properties and that these properties may prove helpful in the treatment of inflammatory diseases of the airways. This review will outline the anti-inflammatory effects of synthetic and endogenous PPAR gamma ligands and discuss their potential therapeutic effects in animal models of inflammatory airway disease. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:101 / 109
页数:9
相关论文
共 66 条
[1]   Benzoyl 2-methyl indoles as selective PPARγ modulators [J].
Acton, JJ ;
Black, RM ;
Jones, AB ;
Moller, DE ;
Colwell, L ;
Doebber, TW ;
MacNaul, KL ;
Berger, J ;
Wood, HB .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (02) :357-362
[2]   Peroxisome proliferator-activated receptor γ inhibits the migration of dendritic cells:: Consequences for the immune response [J].
Angeli, W ;
Hammad, H ;
Staels, B ;
Capron, M ;
Lambrecht, BN ;
Trottein, F .
JOURNAL OF IMMUNOLOGY, 2003, 170 (10) :5295-5301
[3]   An antidiabetic thiazolidinedione induces eccentric cardiac hypertrophy by cardiac volume overload in rats [J].
Arakawa, K ;
Ishihara, T ;
Aoto, M ;
Inamasu, M ;
Kitamura, K ;
Saito, A .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2004, 31 (1-2) :8-13
[4]   Antiinflammatory roles of peroxisome proliferator-activated receptor γ in human alveolar macrophages [J].
Asada, K ;
Sasaki, S ;
Suda, T ;
Chida, K ;
Nakamura, H .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2004, 169 (02) :195-200
[5]   15-Deoxy-Δ12,14-prostaglandin J2 inhibits IL-10 and IL-12 production by macrophages [J].
Azuma, Y ;
Shinohara, R ;
Wang, PL ;
Ohura, K .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 283 (02) :344-346
[6]   New advances and potential therapies for the treatment of asthma [J].
Belvisi, MG ;
Hele, DJ ;
Birrell, MA .
BIODRUGS, 2004, 18 (04) :211-223
[7]   Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-gamma: Binding and activation correlate with antidiabetic actions in db/db mice [J].
Berger, J ;
Bailey, P ;
Biswas, C ;
Cullinan, CA ;
Doebber, TW ;
Hayes, NS ;
Saperstein, R ;
Smith, RG ;
Leibowitz, MD .
ENDOCRINOLOGY, 1996, 137 (10) :4189-4195
[8]   Distinct properties and advantages of a novel peroxisome proliferator-activated protein γ selective modulator [J].
Berger, JP ;
Petro, AE ;
Macnaul, KL ;
Kelly, LJ ;
Zhang, BB ;
Richards, K ;
Elbrecht, A ;
Johnson, BA ;
Zhou, GC ;
Doebber, TW ;
Biswas, C ;
Parikh, M ;
Sharma, N ;
Tanen, MR ;
Thompson, GM ;
Ventre, J ;
Adams, AD ;
Mosley, R ;
Surwit, RS ;
Moller, DE .
MOLECULAR ENDOCRINOLOGY, 2003, 17 (04) :662-676
[9]   PPAR-γ agonists as therapy for diseases involving airway neutrophilia [J].
Birrell, MA ;
Patel, HJ ;
McCluskie, K ;
Wong, S ;
Leonard, T ;
Yacoub, MH ;
Belvisi, MG .
EUROPEAN RESPIRATORY JOURNAL, 2004, 24 (01) :18-23
[10]   PPARγ ligands induce prostaglandin production in vascular smooth muscle cells:: indomethacin acts as a peroxisome proliferator-activated receptor-γ antagonist [J].
Bishop-Bailey, D ;
Warner, TD .
FASEB JOURNAL, 2003, 17 (11) :1925-+