Protein kinase C synergistically stimulates tumor necrosis factor-alpha-induced secretion of urokinase-type plasminogen activator in human dental pulp cells.
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.
Hashizume
Hideki
H
Department of Endodontics, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba, Japan.
Kamio
Naoto
N
Nakao
Sumi
S
Matsushima
Kiyoshi
K
Sugiya
Hiroshi
H
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*
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