title: Tocotrienols reduce 25-hydroxycholesterol-induced monocyte-endothelial cell interaction by inhibiting the surface expression of adhesion molecules.
abstract: The migration of circulating monocytes into the subendothelial space occurs through the expressing of some adhesion molecules on endothelial cells. In the present study, using human aortic endothelial cells (HAECs), we investigated whether a model compound for oxysterols, 25-hydroxycholesterol, can enhance the monocyte adherence to HAECs exposed to 25-hydroxycholesterol via increasing expression of vascular cell adhesion molecule-1 (VCAM-1). We also aimed to determine the in vitro effects of tocotrienols on the enhanced interaction between monocytes and endothelial cells. We found that 25-hydroxycholesterol enhances surface expression determined by ELISA, induces VCAM-1 mRNA expression by real time-PCR, and stimulates adhesiveness of HAECs to U937 monocytic cells in a dose-dependent fashion. The combination treatment with anti-VCAM-1 and anti-CD11b monoclonal antibodies significantly reduced the monocyte adherence to 25-hydroxycholesterol-stimulated HAECs. Compared to alpha-tocopherol, tocotrienols displayed a more profound inhibitory effect on adhesion molecule expression and monocytic cell adherence. We observed that delta-tocotrienol exerted a most profound inhibitory action on monocytic cell adherence when compared to alpha-tocopherol and alpha-, beta-, and gamma-tocotrienols. Tocotrienols accumulated in HAECs to levels approximately 25-95-fold greater than that of alpha-tocopherol. In conclusion, these results indicate that a model compound 25-hydroxycholesterol can enhance the interaction between monocytes and HAECs, and that tocotrienols had a profound inhibitory effect on monocytic cell adherence to HAECs relative to alpha-tocopherol via inhibiting the VCAM-1 expression. These superior inhibitory effects of tocotrienols may be dependent on their intracellular accumulation.
authors.affiliation: Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. ynaito@koto.kpu-m.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimozawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kuroda
authors.forename: Nami
authors.initials: N
authors.lastname: Nakabe
authors.forename: Hiroki
authors.initials: H
authors.lastname: Manabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Norimasa
authors.initials: N
authors.lastname: Yoshida
authors.forename: Noriko
authors.initials: N
authors.lastname: Noguchi
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D024508:Tocotrienols / Q000494:pharmacology*; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D000975:Antioxidants; D006888:Hydroxycholesterols; D012333:RNA, Messenger; D024508:Tocotrienols; D019010:Vascular Cell Adhesion Molecule-1; C007997:25-hydroxycholesterol; D024502:alpha-Tocopherol