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

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.