SOCS1对LIGHT诱导的骨髓来源DC分化成熟的影响  

Effect of the suppressors of cytokine signaling-1(SOCS1) on the differentiation and maturation of bone marrow-derived dendritic cells induced by the TNF superfamily member LIGHT

作　　者：王琪[1] 林苹[1] 张洁[1] 陆燕蓉[2] 王修杰[1] 宁其志[1] 熊竹娟[1] 王静[1] 

机构地区：[1]四川大学华西医院生物治疗国家重点实验室实验肿瘤研究室,成都610041 [2]四川大学华西医院移植工程与移植免疫实验室,成都610041

出　　处：《现代免疫学》2005年第6期456-460,共5页Current Immunology

基　　金：国家自然科学基金资助项目(30270588);四川省应用基础研究资助项目(03JY029-084-2)

摘　　要：为探讨SOCS1是否参与LIGHT诱导的骨髓来源树突状细胞(BmDC)分化成熟,及其在此过程中的作用。RT-PCR检测受LIGHT刺激后小鼠BmDC、小鼠脾脏来源树突状细胞(sDC)中SOCS1mRNA水平及BmDCSOCS1mRNA水平的时间动力学;利用反义核苷酸技术抑制SOCS1的表达,通过流式细胞术(FACS)测定BmDC表面分子CD40、CD86的表达水平来分析阻断SOCS1对LIGHT诱导的BmDC分化成熟的影响。结果显示LIGHT刺激后,BmDCSOCS1mRNA水平迅速增高,并呈峰度变化,在4h时达到高峰;正常无SOCS1mRNA表达的sDC在加LIGHT后可检测到SOCS1mRNA;所设计SOCS1反义寡核苷酸能特异阻断SOCS1mRNA;在LIGHT作用下,SOCS1抑制组较非抑制组的CD40表达明显升高(P<0.05),CD86呈中度升高(P<0.05)。LIGHT在刺激BmDC分化成熟过程中上调了SOCS1的表达,阻断SOCS1使BmDC对LIGHT的反应更敏感,从而使BmDC成熟度更高;SOCS1对LIGHT诱导的BmDC分化成熟有负反馈调节作用。To determine whether SOCS1 could participate the processes of differentiation and maturation of bone marrow-derived dendritic cells（BmDC） induced by the TNF superfamily member LIGHT and the role in these processes, the levels of SOCS1 mRNA in BmDC induced by LIGHT and mouse spleen-derived dendritic cells（sDC） and its time kinetics were investigated in the present study. After blocking the SOCS1 with the anti-sense oligonucleotide technique, the expressions of CD86 and CD40 on DC were measured by flow cytometry to make sure if the silence of SOCS1 would regulate the LIGHT-stimulated maturation of the bone marrow-derived DC. The experimental results showed that with the effect of LIGHT, the level of SOCS1 mRNA in BmDC and sDC all heightened, especially in BmDC with dramatic increase in the expression of SOCS1 mRNA, altered along with the times and peaked at 4 hours. Compared with the SOCS1 unblocked DC, SOCS1-blocked BmDC showed high expres- sions of CD40 and moderate expression of CD86, and enhanced maturation of these cells with stimulation by LIGHT. It is concluded that LIGHT up-regulate the expression of SOSC1 in the course of stimulation in the differentiation and maturation of the BmDC, in which the SOCS-1-blocked BmDC are more sensitive to the effect of LIGHT than the SOCS1-unblocked BmDC, so they have more mature phenotypes. As a whole, SOCS1 presents a negative feedback effect in the maturation of BmDC induced by LIGHT.

关 键 词：LIGHT SOCS1 树突状细胞 

分 类 号：R730[医药卫生—肿瘤]