Curcumin inhibits EMMPRIN and MMP-9 expression through AMPK-MAPK and PKC signaling in PMA induced macrophages

• Published in: Journal of translational medicine 2014-09, Vol.12 (1), p.266-266, Article 266
• Main Authors: Cao, Jiatian, Han, Zhihua, Tian, Lei, Chen, Kan, Fan, Yuqi, Ye, Bozhi, Huang, Weijian, Wang, Changqian, Huang, Zhouqing
• Format: Article
• Language: English
• Subjects: Adenylate Kinase - metabolism; Atherosclerosis; Basigin - drug effects; Basigin - metabolism; Cardiology; Cell culture; Cell Line; Curcumin - pharmacology; Cytotoxicity; Dose-Response Relationship, Drug; Genetic aspects; Grants; Hospitals; Humans; Kinases; Macrophages; Macrophages - drug effects; Macrophages - enzymology; Macrophages - metabolism; Matrix Metalloproteinase 9 - drug effects; Matrix Metalloproteinase 9 - metabolism; Mitogen-Activated Protein Kinases - metabolism; Mitogens; Phosphorylation; Physiological aspects; Physiology; Protein Kinase C - metabolism; Protein kinases; Proteins; Signal Transduction - drug effects; Smooth muscle; Studies; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-014-0266-2

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.