Suppression of skin and kidney disease by inhibition of spleen tyrosine kinase in lupus-prone mice.
Suppression of skin and kidney disease by inhibition of spleen tyrosine kinase in lupus-prone mice.
复制标题
DOI：
10.1002/art.27452
复制
发表时间：
2010-07
影响因子：
--
通讯作者：
Tsokos, George C.
中科院分区：
文献类型：
--
作者：
Deng, Guo-Min;Liu, Lena;Bahjat, Frances Rena;Pine, Polly R.;Tsokos, George C.
脾酪氨酸激酶(Syk)参与包括免疫细胞在内的多种细胞的膜介导信号转导。它在系统性红斑狼疮(SLE)患者的T细胞中过表达，其抑制已被证明可改善(NZB×NZW)F1狼疮小鼠和类风湿关节炎患者的T细胞功能，并改善疾病表现。虽然正在考虑对SLE患者进行Syk抑制的临床试验，但我们实验的目的是确定Syk抑制的治疗效果是否延伸到其他品系的狼疮易感小鼠，以及它们是否导致皮肤病的改善和既定疾病的修改。以雌性MRL/LPR或BAK/BAX小鼠为研究对象。小鼠从出生4周(发病前)或16周(发病后)开始，一直持续到16周，喂食含有Syk抑制剂R788的食物或对照食物。我们发现，在MRL/LPR和BAK/BAX小鼠中抑制Syk可以防止皮肤病的发展，并显著减少已建立的皮肤病。同样，抑制Syk可以缩小脾和淋巴结的大小，抑制肾脏疾病的发展，并抑制已建立的肾脏疾病。停止治疗导致皮肤病被延长抑制至少8周，肾脏疾病被抑制4周。抑制SYK可以抑制狼疮倾向小鼠狼疮皮肤和肾脏疾病的发展，抑制狼疮倾向小鼠已有的疾病，并可能代表SLE患者的一种有价值的治疗方法。
Spleen tyrosine kinase (Syk) is involved in membrane-mediated signaling in various cells, including immune cells. It is overexpressed in T cells from patients with systemic lupus erythematosus (SLE), and its inhibition has been shown to improve T cell function as well as to improve disease manifestations in (NZB × NZW)F1 lupus-prone mice and in patients with rheumatoid arthritis. While clinical trials examining Syk inhibition in patients with SLE are being considered, the aim of our experiments was to determine whether the therapeutic effects of Syk inhibition extend to other strains of lupus-prone mice and whether they result in improvement in skin disease and modification of established disease. Female MRL/lpr or BAK/BAX mice were studied. Starting either at age 4 weeks (before disease) or at age 16 weeks (after established disease) and continuing for up to 16 weeks, mice were fed chow containing the Syk inhibitor R788 or control chow. We found that inhibition of Syk in MRL/lpr and BAK/BAX mice prevented the development of skin disease and significantly reduced established skin disease. Similarly, Syk inhibition reduced the size of the spleen and lymph nodes, suppressed the development of renal disease, and suppressed established renal disease. Discontinuation of treatment resulted in extended suppression of skin disease for at least 8 weeks and suppression of renal disease for 4 weeks. Syk inhibition suppresses the development of lupus skin and kidney disease in lupus-prone mice, suppresses established disease in lupus-prone mice, and may represent a valuable treatment for patients with SLE.
登录
查看更多内容
影响因子：
15.9
作者：
Gao, Cunji;Boylan, Brian;Newman, Peter J.
通讯作者：
Newman, Peter J.
影响因子：
82.9
作者：
Faccio, R;Teitelbaum, SL;Swat, W
通讯作者：
Swat, W
DOI：
10.1124/jpet.106.109058
发表时间：
2006-12-01
影响因子：
3.5
作者：
Braselmann, Sylvia;Taylor, Vanessa;Masuda, Esteban S.
通讯作者：
Masuda, Esteban S.
霍乱毒素B通过促进脂质筏聚集来加速狼疮易发的疾病进展。
DOI：
10.4049/jimmunol.181.6.4019
发表时间：
2008-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Deng GM;Tsokos GC
通讯作者：
Tsokos GC
影响因子：
30.5
作者：
LeibundGut-Landmann, Salome;Gross, Olaf;Sousa, Caetano Reis e
通讯作者：
Sousa, Caetano Reis e