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

摘要

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、1 μM),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 de-rived dendritic cells (DCs) and secretion of MMPs and RANTES. Methods: DCs were cultivated for 8 days with rmGM-CSF. DCs were divided into control and itraconazole (0.25, 0.5, 1 μM) treated groups. The via-bility 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 RAN-TES in the itraconazole group were lower than those in the control group (Ps<0.05). 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.