舒尼替尼抑制树突状细胞表面共刺激分子配体的表达  

Sunitinib inhibits the expressions of co-stimulatory molecule ligands on dendritic cells

作　　者：丁超[1] 麦海星[2] 陈立军[1,2] 张斌[3] 

机构地区：[1]安徽医科大学解放军307医院临床学院泌尿外科 [2]军事医学科学院附属医院泌尿外科,北京100071 [3]军事医学科学院附属医院造血干细胞移植科,北京100071

出　　处：《细胞与分子免疫学杂志》2016年第4期437-441,共5页Chinese Journal of Cellular and Molecular Immunology

基　　金：吴阶平医学基金(32067521203);解放军307医院创新基金(2014)

摘　　要：目的研究舒尼替尼(sunitinib)对肾癌患者外周血单核细胞来源的树突状细胞(DC)表面共刺激分子程序性死亡蛋白配体1(PD-L1)、PD-L2、CD80、CD86、B7-H4及疱疹病毒侵入介体(HVEM)表达的影响。方法体外诱导肾癌患者外周血单核细胞来源的DC,随机分为sunitinib联合LPS组、LPS组及DMSO组。Sunitinib联合LPS组用200 ng/m L sunitinib预处理DC 12 h,再用1μg/m L脂多糖(LPS)刺激24 h;LPS组用1μL/m L DMSO预处理12 h,再用1μg/m L LPS刺激24 h;DMSO组用1μL/m L DMSO作用36 h。倒置显微镜观察各组形态变化;流式细胞术检测DC表面PD-L1、PD-L2、CD80、CD86、B7-H4及HVEM表达变化。结果 Sunitinib联合LPS组和LPS组的DC均呈典型的树枝状突起,DMSO组细胞树突不明显;与LPS组相比,sunitinib联合LPS组表达的CD80、PD-L1及B7-H4显著下降;DMSO组的PD-L1、PD-L2、CD80、CD86、B7-H4及HVEM均呈低水平表达。结论 Sunitinib抑制LPS诱导DC表达CD80、PD-L1、B7-H4。Objective To investigate the effect of sunitinib on the expressions of co-stimulatory molecule ligands,programmed death ligand 1（ PD-L1）,PD-L2,CD80,CD86,B7-H4 and herpes virus entry mediator（ HVEM） on peripheral blood monocyte-derived dendritic cells（ DCs） from patients with renal cel carcinoma（ RCC）. Methods Monocyte-derived DCs from patients with RCC were cultured in vitro and randomly divided into three groups： sunitinib combined with lipopolysaccharide（ LPS）,LPS only and dimethyl sulfoxide（ DMSO） treatment. Sunitinib plus LPS group was pretreated with 200 ng/m L sunitinib for 12 hours followed by stimulated with 1 μg / m L LPS for 24 hours; LPS group was pretreated with 1 μL / m L DMSO for 12 hours and then stimulated with 1 μg / m L LPS for 24 hours; DMSO group was treated with 1 μL / m L DMSO for 36 hours.Morphological changes were observed by an inverted microscope. Flow cytometry was used to detect the expressions of PD-L1,PD-L2,CD80,CD86,B7-H4 and HVEM. Results Sunitinib-LPS co-treated and LPS-treated cells had typical dendrites,while DMSO-treated cells had no obvious dendrites. Compared with the LPS-treated group,the expressions of CD80,PD-L1 and B7-H4 on DCs significantly decreased in the sunitinib-LPS group; the expressions of PD-L1,PD-L2,CD80,CD86,B7-H4 and HVEM were lower in the DMSO group. Conclusion Sunitinib inhibits the expressions of CD80,PD-L1 and B7-H4 on DCs induced by LPS.

关 键 词：舒尼替尼 树突状细胞 共抑制分子 

分 类 号：R392.12[医药卫生—免疫学] R965[医药卫生—基础医学]