title: Luteolin suppresses the differentiation of THP-1 cells through the Inhibition of NOX2 mRNA expression and the membrane translocation of p47phox.
abstract: Luteolin (1), a natural product occurring in many vegetables and fruits, is known to have several biological activities. Cluster for differentiation (CD) families, such as CD11b, -14, and -36, are expressed during pathological processes of atherosclerosis and are used broadly as markers of monocytic differentiation into macrophages. Herein, it was investigated whether 1 and three other flavonoids [chrysin (2), apigenin (3), and tricetin (4)] blocked 12-O-tetradecanoylphorbol 13-acetate (TPA)-triggered induction of CD families, which were induced through the activation of protein kinase C (PKC), mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK), and NADPH oxidase (NOX)-derived reactive oxygen species (ROS). When compared to flavonoids 2-4, 1 blocked TPA-triggered induction of CD families and cell adherence of monocytic THP-1 cells. Luteolin completely blocked intracellular ROS generation, whereas it did not inhibit MEK/ERK phosphorylation. Moreover, pretreatment with 1 suppressed TPA-triggered induction of NOX2 and membrane translocation of p47(phox). Overall, it is revealed that 1 suppresses TPA-triggered induction of CD families by the prevention of NOX2 activation.
authors.affiliation: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Makino
authors.forename: Ryohei
authors.initials: R
authors.lastname: Nakanishi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kamiya
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Mamoru
authors.initials: M
authors.lastname: Koketsu
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
mesh_terms: D047310:Apigenin; D002454:Cell Differentiation / Q000187:drug effects; D002867:Chromones; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015394:Molecular Structure; D009000:Monocytes / Q000187:drug effects; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D002867:Chromones; D005419:Flavonoids; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C043561:chrysin; C469689:tricetin; D047310:Apigenin; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D047311:Luteolin; D013755:Tetradecanoylphorbol Acetate