title: 6-Methylsulfinylhexyl isothiocyanate modulates endothelial cell function and suppresses leukocyte adhesion.
abstract: 6-Methylsulfinylhexyl isothiocyanate (6-MSITC) is an active compound in wasabi (Wasabia japonica Matsum.), which is one of the most popular spices in Japan. 6-MSITC suppresses lipopolysaccharide-induced macrophage activation, arachidonic- or adenosine diphosphate-induced platelet activation, and tumor cell proliferation. These data indicate that 6-MSITC has several biological activities involving anti-inflammatory, anti-coagulant, and anti-apoptosis properties. Endothelial cells (ECs) maintain vascular homeostasis and play crucial roles in crosstalk between blood coagulation and vascular inflammation. In this study, we determined the anti-coagulant and anti-inflammatory effects of 6-MSITC on human umbilical vein endothelial cells (HUVECs). 6-MSITC slightly reduced tissue factor expression, but did not alter von Willebrand factor release in activated HUVECs. 6-MSITC modulated the generation of activated protein C, which is essential for negative regulation of blood coagulation, on normal ECs. In addition, 6-MSITC reduced tumor necrosis factor-α (TNF-α)-induced interleukin-6 and monocyte chemoattractant protein-1 expression. 6-MSITC markedly attenuated TNF-α-induced adhesion of human monoblast U937 cells to HUVECs and reduced vascular cell adhesion molecule-1 and E-selectin mRNA expression in activated ECs. These results showed that 6-MSITC modulates EC function and suppresses cell adhesion. This study provides new insight into the mechanism of the anti-inflammatory effect of 6-MSITC, suggesting that 6-MSITC has therapeutic potential as a treatment for vasculitis and vascular inflammation.
authors.affiliation: Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Okamoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Akita
authors.forename: Masashi
authors.initials: M
authors.lastname: Nagai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011486:Protein C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: C111984:6-methylsulfinylhexyl isothiocyanate; D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019040:E-Selectin; C508600:IL6 protein, human; D015850:Interleukin-6; D017879:Isothiocyanates; D011486:Protein C; D012333:RNA, Messenger; C546936:SELE protein, human; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D013925:Thromboplastin