title: Acacetin inhibits expression of E-selectin on endothelial cells through regulation of the MAP kinase signaling pathway and activation of NF-κB.
abstract: Since E-selectin-mediated adhesion of leukocytes or tumor cells to the vascular endothelium is a key early event in the initiation of inflammatory response and cancer metastasis, E-selectin inhibition is thought to be a good target for therapeutic intervention. Several flavones have been shown to have anti-inflammatory and anticancer properties. In the present study, we investigated the effects of plant flavones on expression of E-selectin in human umbilical vein endothelial cells. Among 11 flavones, acacetin strongly inhibited TNF-α-induced E-selectin expression in HUVECs. Acacetin suppressed the TNF-α-induced phosphorylation of p38 but did not inhibit TNF-α-induced phosphorylations of JNK and ERK. Acacetin also inhibited the activation of NF-κB by stimulation with TNF-α. Furthermore, adhesion of monocytes to TNF-α-treated endothelial cells was inhibited by cotreatment with acacetin. These results suggest that acacetin inhibits the expression of E-selectin by regulation of the p38 MAPK signaling pathway and activation of NF-κB.
authors.affiliation: Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Tanigawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Hagiwara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tada
authors.forename: Toshinori
authors.initials: T
authors.lastname: Komatsu
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Sugiura
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kato
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Ishida
authors.forename: Kyohei
authors.initials: K
authors.lastname: Nishida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Mamoru
authors.initials: M
authors.lastname: Koketsu
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsushita
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D019040:E-Selectin / Q000096:biosynthesis / Q000276:immunology*; D047309:Flavones / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000276:immunology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D020298:U937 Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism
chemical_list: D019040:E-Selectin; D047309:Flavones; D016328:NF-kappa B; C546936:SELE protein, human; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C023717:acacetin