Curcumin inhibits EMMPRIN and MMP-9 expression through AMPK-MAPK and PKC signaling in PMA induced macrophages.
Curcumin inhibits EMMPRIN and MMP-9 expression through AMPK-MAPK and PKC signaling in PMA induced macrophages.
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姜黄素通过 PMA 诱导的巨噬细胞中的 AMPK-MAPK 和 PKC 信号传导抑制 EMMPRIN 和 MMP-9 的表达
DOI：
10.1186/s12967-014-0266-2
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发表时间：
2014-09-21
影响因子：
7.4
通讯作者：
Huang Z
中科院分区：
文献类型：
--
作者：
Cao J;Han Z;Tian L;Chen K;Fan Y;Ye B;Huang W;Wang C;Huang Z
在冠状动脉中，斑块破裂（动脉粥样硬化的主要急性临床表现）导致随后的心脏事件，例如急性心肌梗死（AMI）和不稳定型心绞痛（UA）。大量研究表明，单核/巨噬细胞中基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶-13（MMP-13）和细胞外基质金属蛋白酶诱导因子（EMMPRIN）的高表达导致斑块的进展和不稳定。姜黄素发挥众所周知的抗炎和抗氧化作用，并可能在动脉粥样硬化中具有保护作用。本研究旨在探讨姜黄素对PMA（佛波醇12-肉豆蔻酸酯13-乙酸酯）诱导的巨噬细胞中MMP-9、MMP 13和EMMPRIN的影响及其分子机制。用姜黄素或化合物C预处理人单核细胞（THP-1细胞）1 h，再用PMA诱导48 h。收集总RNA和蛋白质分别用于实时PCR和Western印迹分析。在本研究中，暴露于姜黄素导致减弱JNK，p38和ERK激活，并降低MMP-9，MMP-13和EMMPRIN在PMA诱导的巨噬细胞中的表达。此外，我们证明了AMPK（AMP活化蛋白激酶）和PKC（蛋白激酶C）在单核细胞/巨噬细胞分化过程中被PMA激活。此外，姜黄素逆转PMA刺激的PKC激活，抑制AMPK的慢性激活，从而降低MMP-9，MMP-13和EMMPRIN的表达。因此，姜黄素可能通过抑制丝裂原活化蛋白激酶（AMPK-MAPK）和蛋白激酶C（PKC）途径，下调PMA诱导的THP-1细胞中EMMPRIN、MMP-9和MMP-13的表达。
In coronary arteries, plaque disruption, the major acute clinical manifestations of atherosclerosis, leads to a subsequent cardiac event, such as acute myocardial infarction (AMI) and unstable angina pectoris (UA). Numerous reports have shown that high expression of MMP-9 (matrix metalloproteinase-9), MMP-13 (matrix metalloproteinase-13) and EMMPRIN (extracellular matrix metalloproteinase induce) in monocyte/macrophage results in the plaque progression and destabilization. Curcumin exerts well-known anti-inflammatory and antioxidant effects and probably has a protective role in the atherosclerosis. The purpose of our study was to investigate the molecular mechanisms by which curcumin affects MMP-9, MMP13 and EMMPRIN in PMA (phorbol 12-myristate 13-acetate) induced macrophages. Human monocytic cells (THP-1 cells) were pretreated with curcumin or compound C for 1 h, and then induced by PMA for 48 h. Total RNA and proteins were collected for real-time PCR and Western blot analysis, respectively. In the present study, the exposure to curcumin resulted in attenuated JNK, p38, and ERK activation and decreased expression of MMP-9, MMP-13 and EMMPRIN in PMA induced macrophages. Moreover, we demonstrated that AMPK (AMP-activated protein kinase) and PKC (Protein Kinase C) was activated by PMA during monocyte/macrophage differentiation. Furthermore, curcumin reversed PMA stimulated PKC activation and suppressed the chronic activation of AMPK, which in turn reduced the expression of MMP-9, MMP-13 and EMMPRIN. Therefore, it is suggested that curcumin by inhibiting AMPK-MAPK (mitogen activated protein kinase) and PKC pathway may led to down-regulated EMMPRIN, MMP-9 and MMP-13 expression in PMA-induced THP-1 cells.
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影响因子：
15.9
作者：
GALIS, ZS;SUKHOVA, GK;LIBBY, P
通讯作者：
LIBBY, P
影响因子：
7.7
作者：
Fullerton MD;Steinberg GR
通讯作者：
Steinberg GR
DOI：
10.1161/01.atv.0000021411.53577.1c
发表时间：
2002-07-01
影响因子：
8.7
作者：
Major, TC;Liang, L;Bocan, TMA
通讯作者：
Bocan, TMA
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影响因子：
5
作者：
Meng, S.;Cao, J. -T.;Wang, C. -Q.
通讯作者：
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影响因子：
4.8
作者：
Inokubo, Y;Hanada, H;Okumura, K
通讯作者：
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