title: Protein kinase C synergistically stimulates tumor necrosis factor-alpha-induced secretion of urokinase-type plasminogen activator in human dental pulp cells.
abstract: Plasminogen activator (PA) is the enzyme converting plasminogen to its active form, plasmin, involved in various physiological and pathological phenomena. The conversion is catalyzed by two types of PA, urokinase-type PA (uPA) and tissue-type PA (tPA). When human dental pulp cells were stimulated by the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), PA activity in the conditioned medium was increased, indicating that TNF-alpha provoked PA secretion. The TNF-alpha-induced PA release was significantly enhanced in the presence of phorbol-12-myristate-13-acetate (PMA), a protein kinase C (PKC) activator. The PKC inhibitor Ro31-8220 abolished the effect of PMA on the PA release. The activity of PA secreted from the cells stimulated by TNF-alpha and PMA was reduced by immunoprecipitation using anti-uPA antibody. PMA failed to enhance the TNF-alpha-induced expression of uPA mRNA. These results suggest that protein kinase C synergistically enhances the secretion of uPA in TNF-alpha-stimulated human dental pulp cells.
authors.affiliation: Department of Endodontics, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hashizume
authors.forename: Naoto
authors.initials: N
authors.lastname: Kamio
authors.forename: Sumi
authors.initials: S
authors.lastname: Nakao
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsushima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiya
mesh_terms: D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003782:Dental Pulp / Q000166:cytology / Q000201:enzymology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008963:Molar / Q000166:cytology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D007211:Indoles; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C016658:phorbolol myristate acetate; D011493:Protein Kinase C; D014568:Urokinase-Type Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate; C064758:Ro 31-8220