Halichlorine Reduces Monocyte Adhesion to Endothelium Through the Suppression of Nuclear Factor-κB Activation
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概要
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Halichlorine is a marine alkaloid isolated from the marine sponge Halichondria okadai KADOTA, and its pathophysiological effect on vascular cells remains unknown. Here, we examined the anti-atherosclerosis activity of halichlorine on endothelial cells by assessing the expression of adhesion molecules. In bovine aortic endothelial cells (BAECs), pretreatment with halichlorine (10 μM, 2 h) inhibited lipopolysaccharide (LPS) (3 μg/ml, 3 h)–induced mRNA expressions of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), and E-selectin. Consistently, pretreatment with halichlorine (10 μM, 2 h) reduced LPS (3 μg/ml)–induced monocyte (U937) adhesion to endothelial monolayer. To investigate the mechanism underlying this phenomenon, we examined the effect of halichlorine on nuclear factor-κB (NF-κB) activity in endothelial cells. Treatment with LPS (3 μg/ml) for 1 h increased the ratio of cells showing NF-κB p65 translocation from cytosol to nucleus. Pretreatment with halichlorine (10 μM, 2 h) significantly inhibited the LPS-induced NF-κB p65 translocation. Finally, we examined the cytotoxicity of halichlorine on endothelial cells and found that halichlorine (10 μM, 24 – 48 h) did not influence BAECs proliferation and viability. Herein, we provided the first evidence that halichlorine inhibits LPS-induced NF-κB activation, which results in the suppression of VCAM-1, ICAM-1, and E-selectin gene expression and monocyte-adhesion to endothelial cells.
- 社団法人 日本薬理学会の論文
著者
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YAMADA Kaoru
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University
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UEMURA Daisuke
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University
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Murata Takahisa
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University
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Hori Masatoshi
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University
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Ozaki Hiroshi
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University
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Hori Masatoshi
Department Of Radiology Graduate School Of Medicine Osaka University
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Ozaki Hiroshi
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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Uemura Daisuke
Department Of Biosciences And Informatics Faculty Of Science And Technology Keio University
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Yamada Kaoru
Department Of Biosciences And Informatics Keio University
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Murata Takahisa
Department Of Veterinary Pharmacology Graduate School Of Agriculture And Life Sciences The Universit
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Tsubosaka Yoshiki
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The Univers
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Ozaki Hiroshi
Department Of Electronic Engineering Faculty Of Engineering Osaka University
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