[Resveratrol inhibits expression of EMMPRIN from macrophages].
OBJECTIVE
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.


CONCLUSIONS
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.
Ge
Heng
H
Ren Ji Hospital, Medical School, Shanghai Jiao Tong University, Shanghai 200001, China.
Zhang
Jun-feng
JF
Guo
Bing-shi
BS
He
Ben
B
Wang
Bin-yao
BY
Wang
Chang-qian
CQ
D000813:Anilides / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D051926:Basigin / Q000096:biosynthesis* / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000077205:Pioglitazone; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology; D020298:U937 Cells
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000972:Antineoplastic Agents, Phytogenic; D047495:PPAR gamma; D011993:Recombinant Fusion Proteins; D013267:Stilbenes; D045162:Thiazolidinediones; D051926:Basigin; D008156:Luciferases; D020780:Matrix Metalloproteinase 9; D000077185:Resveratrol; D000077205:Pioglitazone