Document Detail


Artemisinin inhibits extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-9 expression via a protein kinase Cδ/p38/extracellular signal-regulated kinase pathway in phorbol myristate acetate-induced THP-1 macrophages.
MedLine Citation:
PMID:  21039753     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
1. Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinases (MMPs) by monocytes/macrophages has been proposed to play a significant role in atherosclerotic plaque progression and rupture. The aim of the present study was to explore whether artemisinin, a natural extract from Artemisia annua, could decrease EMMPRIN and MMP-9 expression in phorbol myristate acetate (PMA)-induced macrophages by regulating the protein kinase (PK) Cδ/c-Jun N-terminal kinase (JNK)/p38/extracellular signal-regulated kinase (ERK) pathway. 2. Human monocytic THP-1 cells were pretreated with 20-80 μg/mL artemisinin for 4 h or 1-10 μmol/L rottlerin for 1 h prior to stimulation with PMA (100 nmol/L) for another 48 h. Cells were collected to analyse the induction of EMMPRIN and MMP-9. Upstream pathway analysis using the PKCδ inhibitor rottlerin detected activation of the PKCδ/JNK/p38/ERK pathway. 3. Artemisinin (20-80 μg/mL) significantly inhibited the induction of EMMPRIN and MMP-9 at both the transcriptional and translational levels in a dose-dependent manner in PMA-induced macrophages. In addition, artemisinin (20-80 μg/mL) strongly blocked PKCδ/JNK/p38/ERK MAPK phosphorylation. The PKCδ inhibitor rottlerin (1-10 μmol/L) also significantly inhibited JNK/p38/ERK phosphorylation and decreased EMMPRIN and MMP-9 mRNA and protein expression. 4. The results of the present study suggest that artemisinin inhibits EMMPRIN and MMP-9 expression and activity by suppressing the PKCδ/ERK/p38 cascade in PMA-induced macrophages.
Authors:
Yue Wang; Zhou-Qing Huang; Chang-Qian Wang; Lian-Sheng Wang; Shu Meng; Ya-Chen Zhang; Ting Chen; Yu-Qi Fan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  38     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  11-8     Citation Subset:  IM    
Copyright Information:
© 2010 The Authors. Clinical and Experimental Pharmacology and Physiology © 2010 Blackwell Publishing Asia Pty Ltd.
Affiliation:
Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University Medical School, China.
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