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Agonist Rosiglitazone Ameliorates Murine Lupus by Induction of Adiponectin1
* Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118; and
Renal Section, Department of Medicine, Boston University School of Medicine, Boston, MA 02118
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 
(PPAR) 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 agonist rosiglitazone 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 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 agonists.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the National Institutes of Health (PO1 R050256 to I.R.R. and AG15052 to K.W.) and from the Alliance For Lupus Research (to I.R.R.).
2 Address correspondence and reprint requests to Dr. Ian R. Rifkin, Renal Section, Boston University School of Medicine, EBRC 5th Floor, 650 Albany Street, Boston, MA 02118. E-mail address: irifkin{at}bu.edu
3 Abbreviations used in this paper: SLE, systemic lupus erythematosus; PPAR, peroxisome proliferator-activated receptor ; ANA, antinuclear autoantibody.
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  W. Zhao, S. G. Thacker, J. B. Hodgin, H. Zhang, J. H. Wang, J. L. Park, A. Randolph, E. C. Somers, S. Pennathur, M. Kretzler, et al. The Peroxisome Proliferator-Activated Receptor {gamma} Agonist Pioglitazone Improves Cardiometabolic Risk and Renal Inflammation in Murine Lupus J. Immunol., August 15, 2009; 183(4): 2729 - 2740. [Abstract] [Full Text] [PDF]
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