title: Curcumin inhibits EMMPRIN and MMP-9 expression through AMPK-MAPK and PKC signaling in PMA induced macrophages.
abstract: 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.
authors.forename: Jiatian
authors.initials: J
authors.lastname: Cao
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Han
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.forename: Kan
authors.initials: K
authors.lastname: Chen
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Fan
authors.forename: Bozhi
authors.initials: B
authors.lastname: Ye
authors.forename: Weijian
authors.initials: W
authors.lastname: Huang
authors.forename: Changqian
authors.initials: C
authors.lastname: Wang
authors.forename: Zhouqing
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D051926:Basigin / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: C497886:BSG protein, human; D051926:Basigin; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D000263:Adenylate Kinase; D020780:Matrix Metalloproteinase 9; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate