کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3884846 1249492 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Increased survival and reduced renal injury in MRL/lpr mice treated with a novel sphingosine-1-phosphate receptor agonist
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
پیش نمایش صفحه اول مقاله
Increased survival and reduced renal injury in MRL/lpr mice treated with a novel sphingosine-1-phosphate receptor agonist
چکیده انگلیسی

Agonists of the type 1 sphingosine-1-phosphate (S1P) receptor inhibit lymphocyte migration, causing their sequestration in lymphoid tissue. The S1P agonist FTY720 prolongs the survival of organ allografts and blocks T-cell mediated autoimmune diseases in experimental models; however, it is a non-selective agonist of four of the five S1P receptors. In this study female MRL/lpr mice, which develop an aggressive form of spontaneous autoimmune kidney disease, were treated with a more selective agonist of the type 1 receptor (KRP-203) or vehicle at 12 or 16 weeks of age. Eighty percent of the mice treated at 12 weeks, before the onset of visible disease, survived to the 24 weeks end point with decreased tubulointerstitial disease and significantly fewer infiltrating CD4+ and CD8+ T-cells. Only half of the control vehicle-treated mice survived. All of the mice treated at 16 weeks survived with reduced proteinuria. Mice in both groups had significant reductions in circulating lymphocytes. Mice receiving KRP-203 for 8–12 weeks had significant reductions in T-cells and consequently less adenopathy. Ex vivo treatment of lymphocytes from MRL/lpr mice with KRP-203 enhanced their apoptosis. Our study indicates that KRP-203 attenuates kidney injury in MRL/lpr mice, in part, by reducing T-cell infiltrates.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 74, Issue 10, 2 November 2008, Pages 1319–1326
نویسندگان
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