白藜芦醇抑制巨噬细胞细胞外基质金属蛋白酶诱导物的表达  

Resveratrol inhibits expression of EMMPRIN from macrophages

作　　者：葛恒[1] 张俊峰[2] 郭炳诗 何奔[1] 王彬尧[1] 王长谦[1] 

机构地区：[1]上海交通大学医学院附属仁济医院,上海200001 [2]上海交通大学医学院附属第三人民医院,上海201900 [3]上海市健康科学中心,上海200025

出　　处：《药学学报》2006年第7期625-630,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30070869).

摘　　要：目的探讨白藜芦醇对细胞外基质金属蛋白酶诱导物(EMMPR IN)表达的影响。方法将人类单核细胞系THP-1和MCF-7细胞共培养,测定上清液中MMP-9活性。用PMA诱导THP-1为巨噬细胞,加入白藜芦醇,观察EMMPR IN表达和MMP-9活性变化。细胞共转染实验测定白藜芦醇对PPARγ的激动作用。用PPARγ的拮抗剂GW 9662预处理细胞后,测定白藜芦醇对EMMPR IN表达的影响。结果PMA诱导使单核细胞EMMPR IN表达明显增强,与EMMPR IN高表达的MCF-7细胞共培养显著增加单核细胞表达MMP-9。白藜芦醇显著抑制EMMPR IN和MMP-9生成。白藜芦醇明显激动PPAR,γGW 9662大幅减弱白藜芦醇对EMMPR IN和MMP-9的作用。结论单核细胞向巨噬细胞分化过程中表达明显增强的EMMPR IN可能是促进MMPs表达的主要因子。白藜芦醇通过激动PPARγ抑制EMMPR IN的表达,可能是其抑制巨噬细胞MMPs产生的机制。Aim To investigate the effect of resveratrol on EMMPRIN Methods Human monocytic cell line THP-1 cells were co-cultured with expression of macrophages. EMMPRIN-highly-expressed MCF-7 cells; MMP-9 production was assayed by zymography. THP-1 cells were induced by PMA, expression of EMMPRIN was assayed by Western blotting. Cells were treated with resveratrol or PPART agonist - pioglitazone during differentiation, EMMPRIN expression and MMP-9 activity were assayed. U937 cells were co-transfected with PPART expression and luciferase-coding reporter vector, then cultured with pioglitazone or resveratrol, the activating capability of resveratrol on PPART was evaluated by measuring the luciferase activity. THP-1 cells were pretreated with PPARγ antagonist - GW9662 before pioglitazone or resveratrol treatment, then assayed for EMMPRIN expression and MMP-9 production. Results EMMPRIN expression was greatly increased during the differentiation from monocytes to macrophages; co-culturing with MCF-7 cells significantly increased MMP-9 production by monocytes. Both resveratrol and pioglitazone markedly inhibited EMMPRIN expression during monocytes differentiation. Resveratrol significantly activated PPART and GW9662 greatly decreased the effect of resveratrol on EMMPRIN and MMP-9. Conclusion EMMPRIN expression is greatly up-regulated from monocytes to macrophages, which may play a role in inducing MMPs production by monocytes/macrophages. Resveratrol can significantly inhibit EMMPRIN expression via activating PPARγ, which may be the underlying mechanism of its inhibitory effect on MMPs production by monocytes/macrophages.

关 键 词：细胞外基质金属蛋白酶诱导物 过氧化物酶体增殖剂激活受体γ 基质金属蛋白酶 白藜芦醇 单核/巨噬细胞 

分 类 号：R963[医药卫生—微生物与生化药学]