FTY720 exerts a survival advantage through the prevention of end-stage glomerular inflammation in lupus-prone BXSB mice
FTY720 exerts a survival advantage through the prevention of end-stage glomerular inflammation in lupus-prone BXSB mice
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DOI：
10.1016/j.bbrc.2010.03.078
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发表时间：
2010-04-09
影响因子：
3.1
通讯作者：
Takasaki, Yoshinari
中科院分区：
文献类型：
--
作者：
Ando, Seiichiro;Amano, Hirofumi;Takasaki, Yoshinari
FTY 720是一种靶向1-磷酸鞘氨醇（SIP）受体的新型研究药物，具有通过诱导淋巴器官中的淋巴细胞隔离引起免疫抑制的能力。系统性红斑狼疮（SLE）是难治性自身免疫性疾病，其特征在于产生多种自身抗体和免疫复合物（IC）介导的狼疮性肾炎。BXSB在与疾病相关的外周单核细胞增多和脾脏边缘区B（MZ B）细胞频率降低方面是独特的。在本研究中，我们检测了FIY 720对BXSB小鼠狼疮性肾炎的影响。并引起边缘区B（MZ B）细胞重新定位到脾中的滤泡中。这些变化不影响自身抗体的产生，因此IgG和C3沉积在FTY 720处理的小鼠的肾小球中。尽管有这些IC沉积，FTY 720治疗的小鼠表现出生存优势，蛋白尿改善组织学分析显示，FTY 720抑制肾小球系膜细胞增殖和炎性细胞浸润这些结果表明，FTY 720通过抑制肾小球IC沉积后的终末期炎症过程来改善狼疮肾炎（C）2010 Elsevier Inc版权所有
FTY720 is a novel investigational agent targeting the sphingosine 1-phosphate (SIP) receptors with an ability to cause immunosuppression by inducing lymphocyte sequestration in lymphoid organs Systemic lupus erythematosus (SLE) is refractory autoimmune disease characterized by the production of a wide variety of autoantibodies and immune complex (IC)-mediated lupus nephritis Among several SLE-prone strains of mice. BXSB is unique in terms of the disease-associated monocytosis in periphery and the reduced frequency of marginal zone B (MZ B) cells in spleen In the present study, we examined the effect of FIY720 on lupus nephritis of BXSB mice FTY720 treatment resulted in a marked decrease in lymphocytes, but not monocytes, in peripheral blood, and caused relocalization of marginal zone B (MZ B) cells into the follicle in the spleen These changes did not affect the production of autoantibodies, thus IgG and C3 were deposited in glomeruli in FTY720-treated mice Despite these IC depositions, FTY720-treated mice showed survival advantage with the improved proteinuria Histological analysis revealed that FTY720 suppressed mesangial cell proliferation and inflammatory cell infiltration These results suggest that FTY720 ameliorates lupus nephritis by inhibiting the end-stage inflammatory process following IC deposition in glomeruli (C) 2010 Elsevier Inc All rights reserved