亲环素A启动单核细胞炎症性募集的机制

Mechanism of Cyclophilin A Initiating the Inflammatory Recruitment of Monocytes

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α(TNF-α)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;Western blot检测核因子κB(NF-κB)炎症信号通路、丝裂原活化蛋白激醇(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-κB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.