| 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. | |
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MedLine Citation:
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PMID: 21039753 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical and experimental pharmacology & physiology Volume: 38 ISSN: 1440-1681 ISO Abbreviation: Clin. Exp. Pharmacol. Physiol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-04 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0425076 Medline TA: Clin Exp Pharmacol Physiol Country: Australia |
Other Details:
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Languages: eng Pagination: 11-8 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors. Clinical and Experimental Pharmacology and Physiology © 2010 Blackwell Publishing Asia Pty Ltd. |
Affiliation:
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Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University Medical School, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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