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

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。

Resveratrol inhibits expression of EMMPRIN from macrophages

AIM: To investigate the effect of resveratrol on EMMPRIN expression of macrophages. METHODS: Human 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 PPARgamma agonist--pioglitazone during differentiation, EMMPRIN expression and MMP-9 activity were assayed. U937 cells were co-transfected with PPARy expression and luciferase-coding reporter vector, then cultured with pioglitazone or resveratrol, the activating capability of resveratrol on PPARgamma was evaluated by measuring the luciferase activity. THP-1 cells were pretreated with PPARgamma 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 PPARgamma 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 PPARgamma, which may be the underlying mechanism of its inhibitory effect on MMPs production by monocytes/macrophages.