葛恒, 张俊峰, 郭炳诗, 何奔, 王彬尧, 王长谦. 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J. 药学学报, 2006, 41(7): 625-630.
引用本文: 葛恒, 张俊峰, 郭炳诗, 何奔, 王彬尧, 王长谦. 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J. 药学学报, 2006, 41(7): 625-630.
GE Heng, ZHANG Jun-feng, GUO Bing-shi, HE Ben, WANG Bin-yao, WANG Chang-qian. Resveratrol inhibits expression of EMMPRIN from macrophagesJ. Acta Pharmaceutica Sinica, 2006, 41(7): 625-630.
Citation: GE Heng, ZHANG Jun-feng, GUO Bing-shi, HE Ben, WANG Bin-yao, WANG Chang-qian. Resveratrol inhibits expression of EMMPRIN from macrophagesJ. Acta Pharmaceutica Sinica, 2006, 41(7): 625-630.

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

  • 摘要: 目的探讨白藜芦醇对细胞外基质金属蛋白酶诱导物(EMMPRIN)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EMMPRIN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GW9662预处理细胞后,测定白藜芦醇对EMMPRIN表达的影响。结果PMA诱导使单核细胞EMMPRIN表达明显增强,与EMMPRIN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EMMPRIN和MMP-9生成。白藜芦醇明显激动PPARγ,GW9662大幅减弱白藜芦醇对EMMPRIN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EMMPRIN可能是促进MMPs表达的主要因子。白藜芦醇通过激动PPARγ抑制EMMPRIN的表达,可能是其抑制巨噬细胞MMPs产生的机制。

     

    Abstract: AimTo investigate the effect of resveratrol on EMMPRIN expression of macrophages. MethodsHuman monocytic cell line THP-1 cells were co-cultured with 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 PPARγ agonist — pioglitazone during differentiation, EMMPRIN expression and MMP-9 activity were assayed. U937 cells were co-transfected with PPARγ expression and luciferase-coding reporter vector, then cultured with pioglitazone or resveratrol, the activating capability of resveratrol on PPARγ 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. ResultsEMMPRIN 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 PPARγ and GW9662 greatly decreased the effect of resveratrol on EMMPRIN and MMP-9. ConclusionEMMPRIN 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.

     

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