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.