title: 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.affiliation: Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tsubosaka
authors.forename: Takahisa
authors.initials: T
authors.lastname: Murata
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yamada
authors.forename: Daisuke
authors.initials: D
authors.lastname: Uemura
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ozaki
mesh_terms: D000470:Alkaloids / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009994:Osmolar Concentration; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013141:Spiro Compounds / Q000009:adverse effects / Q000494:pharmacology*; D013997:Time Factors; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D019040:E-Selectin; D016328:NF-kappa B; D012333:RNA, Messenger; D013141:Spiro Compounds; D019010:Vascular Cell Adhesion Molecule-1; C412666:halichlorine; D018799:Intercellular Adhesion Molecule-1