Title |
A Dexamethasone Prodrug Reduces the Renal Macrophage Response and Provides Enhanced Resolution of Established Murine Lupus Nephritis
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Published in |
PLOS ONE, November 2013
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DOI | 10.1371/journal.pone.0081483 |
Pubmed ID | |
Authors |
Fang Yuan, Dana E. Tabor, Richard K. Nelson, Hongjiang Yuan, Yijia Zhang, Jenny Nuxoll, Kimberly K. Bynoté, Subodh M. Lele, Dong Wang, Karen A. Gould |
Abstract |
We evaluated the ability of a macromolecular prodrug of dexamethasone (P-Dex) to treat lupus nephritis in (NZB × NZW)F1 mice. We also explored the mechanism underlying the anti-inflammatory effects of this prodrug. P-Dex eliminated albuminuria in most (NZB × NZW)F1 mice. Furthermore, P-Dex reduced the incidence of severe nephritis and extended lifespan in these mice. P-Dex treatment also prevented the development of lupus-associated hypertension and vasculitis. Although P-Dex did not reduce serum levels of anti-dsDNA antibodies or glomerular immune complexes, P-Dex reduced macrophage recruitment to the kidney and attenuated tubulointerstitial injury. In contrast to what was observed with free dexamethasone, P-Dex did not induce any deterioration of bone quality. However, P-Dex did lead to reduced peripheral white blood cell counts and adrenal gland atrophy. These results suggest that P-Dex is more effective and less toxic than free dexamethasone for the treatment of lupus nephritis in (NZB × NZW)F1 mice. Furthermore, the data suggest that P-Dex may treat nephritis by attenuating the renal inflammatory response to immune complexes, leading to decreased immune cell infiltration and diminished renal inflammation and injury. |
X Demographics
Geographical breakdown
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United States | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 17 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Other | 3 | 18% |
Student > Bachelor | 3 | 18% |
Student > Doctoral Student | 2 | 12% |
Student > Ph. D. Student | 2 | 12% |
Student > Master | 2 | 12% |
Other | 3 | 18% |
Unknown | 2 | 12% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 7 | 41% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 18% |
Agricultural and Biological Sciences | 3 | 18% |
Immunology and Microbiology | 1 | 6% |
Unknown | 3 | 18% |