Resveratrol inhibits matrix metalloproteinase-9 transcription in U937 cells.
OBJECTIVE
To examine the inhibitory effect of resveratrol on matrix metalloroteinase-9 (MMP-9) and explore its mechanism.


METHODS
MMP-9 activity was analyzed by gelatin zymography; MMP-9 protein was detected by Western blot; MMP-9 mRNA expression was investigated by RT-PCR. Activation of activator protein -1 (AP-1) was measured by electrophoretic mobility shift assay (EMSA).


RESULTS
MMP-9 activity in U937 cells increased significantly after exposed to PMA at 10 nmol/L for 24 h without FCS (P<0.01). Resveratrol at 1 and 10 micromol/L showed significant inhibition on MMP-9 activity (P<0.05 and P<0.01, respectively). Western blot and RT-PCR experiments displayed that MMP-9 protein (P<0.01) and mRNA expression (P<0.01) increased significantly in PMA-treated U937 cells. Resveratrol at 1 and 10 micromol/L showed inhibitory effects on MMP-9 protein production and MMP-9 mRNA expression (P<0.05). The activation of AP-1 induced by PMA was also extensively inhibited by resveratrol at 0.1, 1, and 10 micromol/L.


CONCLUSIONS
The inhibitory effect of resveratrol on MMP-9 activity may be partly through suppression of activation of nuclear transcription factor AP-1, and inhibition of MMP-9 mRNA expression and MMP-9 protein production.
Li
Yi-Tang
YT
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Shen
Fang
F
Liu
Bai-He
BH
Cheng
Gui-Fang
GF
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic; D020298:U937 Cells
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012333:RNA, Messenger; D013267:Stilbenes; D018808:Transcription Factor AP-1; D003907:Dexamethasone; D020780:Matrix Metalloproteinase 9; D000077185:Resveratrol