Caffeine induces matrix metalloproteinase-2 (MMP-2) and MMP-9 down-regulation in human leukemia U937 cells via Ca2+/ROS-mediated suppression of ERK/c-fos pathway and activation of p38 MAPK/c-jun pathway
Article first published online: 28 APR 2010
Copyright © 2010 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 224, Issue 3, pages 775–785, September 2010
How to Cite
Liu, W.-H. and Chang, L.-S. (2010), Caffeine induces matrix metalloproteinase-2 (MMP-2) and MMP-9 down-regulation in human leukemia U937 cells via Ca2+/ROS-mediated suppression of ERK/c-fos pathway and activation of p38 MAPK/c-jun pathway. J. Cell. Physiol., 224: 775–785. doi: 10.1002/jcp.22180
- Issue published online: 25 JUN 2010
- Article first published online: 28 APR 2010
- Manuscript Accepted: 18 MAR 2010
- Manuscript Received: 12 JAN 2010
- National Science Council, ROC. Grant Number: NSC98-2320-B110-002-MY3
- National Sun Yat-Sen University–Kaohsiung Medical University Joint Research Center
Caffeine attenuated invasion of human leukemia U937 cells with characteristic of decreased protein expression and mRNA levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. Down-regulation of MMP-2 and MMP-9 in U937 cells was abrogated by abolishment of caffeine-elicited increase in intracellular Ca2+ concentration and ROS generation. Pretreatment with BAPTA-AM (Ca2+ chelator) and N-acetylcysteine (ROS scavenger) abolished caffeine-induced ERK inactivation and p38 MPAK activation. Moreover, caffeine treatment led to MAPK phosphatase-1 (MKP-1) down-regulation and protein phosphatase 2A catalytic subunit (PP2Ac) up-regulation, which were involved in cross-talk between p38 MAPK and ERK. Transfection of constitutively active MEK1 or pretreatment with SB202190 (p38 MAPK inhibitor) restored MMP-2 and MMP-9 protein expression in caffeine-treated cells. Caffeine treatment repressed ERK-mediated c-Fos phosphorylation but evoked p38 MAPK-mediated c-Jun phosphorylation. Knock-down of c-Fos and c-Jun by siRNA reflected that c-Fos counteracted the effect of c-Jun on MMP-2/MMP-9 down-regulation. Taken together, our data indicate that MMP-2/MMP-9 down-regulation in caffeine-treated U937 cells is elicited by Ca2+/ROS-mediated suppression of ERK/c-Fos pathway and activation of p38 MAPK/c-Jun pathway. J. Cell. Physiol. 224: 775–785, 2010. © 2010 Wiley-Liss, Inc.