Get access

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

Authors

  • Wen-Hsin Liu,

    1. Institute of Biomedical Sciences, National Sun Yat-Sen University–Kaohsiung Medical University Joint Research Center, National Sun Yat-Sen University, Kaohsiung, Taiwan
    Search for more papers by this author
  • Long-Sen Chang

    Corresponding author
    1. Institute of Biomedical Sciences, National Sun Yat-Sen University–Kaohsiung Medical University Joint Research Center, National Sun Yat-Sen University, Kaohsiung, Taiwan
    • Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
    Search for more papers by this author

Abstract

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.

Ancillary