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
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
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DOI：
10.1002/jcp.22180
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发表时间：
2010-09-01
影响因子：
5.6
通讯作者：
Chang, Long-Sen
中科院分区：
文献类型：
--
作者：
Liu, Wen-Hsin;Chang, Long-Sen
咖啡因通过降低基质金属蛋白酶-2 （MMP-2）和MMP-9的蛋白表达和mRNA水平来减弱人白血病U937细胞的侵袭。在U937细胞中，MMP-2和MMP-9的下调通过消除咖啡因引起的细胞内Ca2+浓度和ROS生成的增加而被消除。用BAPTA-AM （Ca2+螯合剂）和n -乙酰半胱氨酸（ROS清除剂）预处理可消除咖啡因诱导的ERK失活和p38 MPAK活化。此外，咖啡因处理导致MAPK磷酸酶-1 （MKP-1）下调和蛋白磷酸酶2A催化亚基（PP2Ac）上调，这参与了p38 MAPK和ERK之间的串扰。转染组成活性MEKI或用SB202190 （p38 MAPK抑制剂）预处理可以恢复咖啡因处理细胞中MMP-2和MMP-9蛋白的表达。咖啡因抑制了erk介导的c-Fos磷酸化，但激发了p38 mapk介导的c-Jun磷酸化。c-Fos和c-Jun被siRNA敲低反映c-Fos抵消了c-Jun对MMP-2/MMP-9下调的影响。综上所述，我们的数据表明，在咖啡因处理的U937细胞中，MMP-2/MMP-9的下调是通过Ca2+/ ros介导的ERK/c-Fos通路的抑制和p38 MAPK/c-Jun通路的激活引起的。j .细胞。中国生物医学工程学报，2009,31(2):775-785。(C) 2010 Wiley-Liss, Inc。
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-I (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 MEKI 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. (C) 2010 Wiley-Liss, Inc.