Halichlorine reduces monocyte adhesion to endothelium through the suppression of nuclear factor-kappaB activation.

Abstract

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 microM, 2 h) inhibited lipopolysaccharide (LPS) (3 microg/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 microM, 2 h) reduced LPS (3 microg/ml)-induced monocyte (U937) adhesion to endothelial monolayer. To investigate the mechanism underlying this phenomenon, we examined the effect of halichlorine on nuclear factor-kappaB (NF-kappaB) activity in endothelial cells. Treatment with LPS (3 microg/ml) for 1 h increased the ratio of cells showing NF-kappaB p65 translocation from cytosol to nucleus. Pretreatment with halichlorine (10 microM, 2 h) significantly inhibited the LPS-induced NF-kappaB p65 translocation. Finally, we examined the cytotoxicity of halichlorine on endothelial cells and found that halichlorine (10 microM, 24 - 48 h) did not influence BAECs proliferation and viability. Herein, we provided the first evidence that halichlorine inhibits LPS-induced NF-kappaB activation, which results in the suppression of VCAM-1, ICAM-1, and E-selectin gene expression and monocyte-adhesion to endothelial cells.

• Authors: Yoshiki Tsubosaka, Takahisa Murata, Kaoru Yamada, Daisuke Uemura, Masatoshi Hori, Hiroshi Ozaki
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 113 Issue 3 Pg. 208-13 ( 2010) ISSN: 1347-8648 [Electronic] Japan
• PMID: 20562517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Anti-Inflammatory Agents, Non-Steroidal
• E-Selectin
• NF-kappa B
• RNA, Messenger
• Spiro Compounds
• Vascular Cell Adhesion Molecule-1
• halichlorine
• Intercellular Adhesion Molecule-1

Topics

• Alkaloids (adverse effects, pharmacology)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (adverse effects, pharmacology)
• Atherosclerosis (drug therapy)
• Cattle
• Cell Adhesion (drug effects)
• Cell Nucleus (drug effects, metabolism)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Down-Regulation (drug effects)
• E-Selectin (genetics, metabolism)
• Endothelial Cells (drug effects, metabolism)
• Humans
• Intercellular Adhesion Molecule-1 (genetics, metabolism)
• Monocytes (drug effects)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Osmolar Concentration
• Protein Transport (drug effects)
• RNA, Messenger (metabolism)
• Spiro Compounds (adverse effects, pharmacology)
• Time Factors
• U937 Cells
• Vascular Cell Adhesion Molecule-1 (genetics, metabolism)