Abstract
The adhesion of monocytes to human umbilical vein endothelial cells (HUVECs) plays a crucial role in the initiation of atherosclerosis. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are two important molecules involved in the adhesion of monocytes to HUVECs. Previous studies have suggested that artemisinin, apart from an anti-malarial agent, also has other effects. In the present study, we found that artemisinin significantly decreased the adhesion of monocytes to tumor necrosis factor-α (TNF-α)-stimulated HUVECs in a dose-dependent manner and suppressed the mRNA and protein level of ICAM-1 and VCAM-1 in the TNF-α-stimulated HUVECs. In addition, the nuclear factor-κB (NF-κB) inhibitor, Bay 11-7082, and mitogen-activated protein kinase (MAPK) inhibitors (SB203580 and U0126) respectively reduced the adhesion of monocytes to TNF-α-stimulated HUVECs, and suppressed ICAM-1 and VCAM-1 expression in TNF-α stimulated HUVECs. Moreover, artemisinin impeded the activation of the NF-κB and MAPK signaling pathways. Furthermore, Bay 11-7082 significantly decreased the phosphorylation of levels extracellular signal-regulated protein kinase (ERK)1/2, p38 and c-Jun N-terminal kinase (JNK). Taken together, the findings of our study indicated that artemisinin blocked monocyte adhesion to TNF-α-stimulated to HUVECs by downregulating ICAM-1 and VCAM-1 expression in the TNF-α-stimulated HUVECs. Artemisinin may thus have potential for use in the protection against the early development of atherosclerotic lesions.
MeSH terms
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Anti-Inflammatory Agents / pharmacology*
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Artemisinins / pharmacology*
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Butadienes / pharmacology
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Cell Adhesion / drug effects
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Cell Line
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Coculture Techniques
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Gene Expression Regulation
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Human Umbilical Vein Endothelial Cells
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Humans
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Imidazoles / pharmacology
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
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JNK Mitogen-Activated Protein Kinases / genetics*
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JNK Mitogen-Activated Protein Kinases / metabolism
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / genetics*
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 3 / genetics*
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Mitogen-Activated Protein Kinase 3 / metabolism
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Monocytes / cytology
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Monocytes / drug effects*
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Monocytes / metabolism
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NF-kappa B / genetics*
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NF-kappa B / metabolism
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Nitriles / pharmacology
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Phosphorylation / drug effects
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Protein Kinase Inhibitors / pharmacology
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Pyridines / pharmacology
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Signal Transduction
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Sulfones / pharmacology
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / pharmacology
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Vascular Cell Adhesion Molecule-1 / genetics
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Vascular Cell Adhesion Molecule-1 / metabolism
Substances
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3-(4-methylphenylsulfonyl)-2-propenenitrile
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Anti-Inflammatory Agents
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Artemisinins
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Butadienes
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ICAM1 protein, human
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Imidazoles
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NF-kappa B
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Nitriles
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Protein Kinase Inhibitors
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Pyridines
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Sulfones
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Tumor Necrosis Factor-alpha
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U 0126
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Vascular Cell Adhesion Molecule-1
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Intercellular Adhesion Molecule-1
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artemisinin
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JNK Mitogen-Activated Protein Kinases
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MAPK1 protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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SB 203580