伊曲康唑抑制小鼠树突状细胞迁移及MMP-2、MMP-3、MMP-12与RANTES的分泌

Itraconazole inhibited the migration of murine bone marrow derived dendritic cells and secretion of MMP-2,MMP-3,MMP-12 and RANTES

目的:明确伊曲康唑对小鼠骨髓来源树突状细胞(DCs)迁移功能及基质金属蛋白酶(MMP)-2、MMP-3、MMP-12与趋化因子RANTES分泌的影响。方法:取小鼠骨髓单核细胞,重组小鼠粒-巨噬细胞集落刺激因子(rmGM-CSF)诱导至第8天,将DCs分为对照组、伊曲康唑处理组(0.25、0.5、1μM),细胞计数试剂盒(CCK-8)和Transwell分别检测不同浓度伊曲康唑对DCs活性及DCs迁移情况;Luminex液相芯片技术检测MMP-2、MMP-3、MMP-8、MMP-12、CCL5/RANTES的分泌;流式细胞仪检测MHCII、CD40、CD80、CD86及CCR7的表达。结果:伊曲康唑对树突状细胞毒性呈时间及剂量依赖;伊曲康唑组细胞迁移率低于对照组,差异有统计学意义(P<0.05)。伊曲康唑组MMP-2、MMP-3、MMP-12和RANTES水平均低于对照组,差异均有统计学意义(均P<0.05)。伊曲康唑组和对照组中的CCR7和MMP-8水平差异无统计学意义(P>0.05)。结论:伊曲康唑抑制树突状细胞的迁移及相关MMPs和趋化因子的表达。

Objective： To determine the effects of itraconazole on the migration of murine bone marrow derived dendritic cells（ DCs） and secretion of MMPs and RANTES. Methods： DCs were cultivated for 8 days with rm GM-CSF. DCs were divided into control and itraconazole（ 0.25,0.5,1 μM） treated groups. The viability and migration of DCs were determined by CCK-8 assay and transwell assay respectively. The levels of MMP-2,MMP-3,MMP-8,MMP-12 and RANTES were detected by Luminex. The levels of MHCII,CD40,CD80,CD86 and CCR7 were measured by flow cytometry. Results： The cytotoxicity of itraconazole on DCs was time and dose-dependent. The migration rate and levels of MMP-2,MMP-3,MMP-12 and RANTES in the itraconazole group were lower than those in the control group（ Ps0.05）. There was no significant difference of the level of CCR and MMP-8 in two groups（ P〉0.05）. Conclusion： Itraconazole inhibited the DCs cell migration and secretion of MMPs and RANTES.