The Peroxisome Proliferator-Activated Receptor γ Agonist Rosiglitazone Ameliorates Murine Lupus by Induction of Adiponectin

被引:83
作者
Aprahamian, Tamar [1 ,2 ]
Bonegio, Ramon G. [1 ]
Richez, Christophe [1 ]
Yasuda, Kei [1 ]
Chiang, Lo-Ku [1 ]
Sato, Kaori [2 ]
Walsh, Kenneth [2 ]
Rifkin, Ian R. [1 ]
机构
[1] Boston Univ, Sch Med, Renal Sect, Dept Med, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA
基金
美国国家卫生研究院;
关键词
C-REACTIVE PROTEIN; INSULIN-RESISTANCE; ADIPOSE-TISSUE; PPAR-GAMMA; SERUM LEPTIN; DRUG-THERAPY; INFLAMMATION; PLASMA; ASSOCIATION; LIGANDS;
D O I
10.4049/jimmunol.182.1.340
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease for which current therapy is suboptimal. SLE is characterized by autoantibody production, with renal disease and premature atherosclerosis being common and severe manifestations causing appreciable morbidity and mortality. Peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists are widely used in the treatment of diabetes mellitus for their insulin-sensitizing properties, but also have immunomodulatory effects. In this report, we show that the PPAR gamma agonist rosiglitatzone reduces autoantibody production, renal disease, and atherosclerosis in mouse models of SLE. The beneficial effect of rosiglitazone on SLE manifestations depends on the induction of adiponectin, because rosiglitazone has no effect on autoantibody production or renal disease in lupus mice that lack adiponectin. In addition, lupus mice that lack adiponectin develop more severe disease than adiponectin-sufficient lupus mice, indicating that endogenous adiponectin is involved in regulating disease activity. Furthermore, administration of exogenous adiponectin ameliorates disease. These experiments suggest that PPAR gamma agonists may be useful agents for the treatment of SLE. They also demonstrate that induction of adiponectin is a major mechanism underlying the immunomodulatory effects of PPAR gamma agonists. The Journal of Immunology, 2009,182: 340-346.
引用
收藏
页码:340 / 346
页数:7
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