目的探讨亲环素A在单核细胞参与氧化应激炎症反应中的作用。方法人类单核细胞系THP-1细胞常规体外培养,以亲环素A作为氧化应激炎症反应的主要活性氧诱导刺激因子,Transwell法检测亲环素A对单核细胞迁移趋化的影响;ELISA检测单核细胞培养液中主要炎症反应因子白细胞介素6(IL-6)、肿瘤坏死因子仪(TNF.d)的含量变化;明胶酶谱法测定基质金属蛋白酶9(MMP-9)的活性变化;Westernblot检测核因子KB(NF—KB)炎症信号通路、丝裂原活化蛋白激酶(MAPK)炎症信号通路的激活。结果亲环素A可以诱导单核细胞迁移趋化.促进单核细胞分泌炎症反应因子IL-6;亲环素A通过MAPK-NF—KB炎症信号通路增强MMP-9活性。结论亲环素A诱导单核细胞迁移趋化,促进单核细胞分泌炎症因子,显示了其启动单核细胞炎症性募集的作用。
Aim To investigate the role of cyclophilin A (CypA) in the inflammatory respbnse of monocytes. Methods Human monocytic cell line THP-1 ceils were cultured. Human recombinant CypA was added as indicated. Chemotactic activity was assessed in transwell chamber. Tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) were detected by ELISA. Matrix metalloproteinase-9 (MMP-9) activity was determined by gel zymography. The protein ex- pression of nuclear factor-KB (NF-KB) and mitogen-activated protein kinase (MAPK) were detected by Western blot. Results CypA strongly induced migration of monocytes and the expression of MMP-9, IL-6. The cascade of ERK-NF-KB was the main signaling pathway for CypA-induced MMP-9 production in monocytes/macrophages. Conclusions CypA induced migration of monocytes and the expression of pro-inflammatory cytokines. These findings suggest that pro-inflam- matory activities are induced by CypA in monocytes.