title: Tumor necrosis factor α stimulates expression and secretion of urokinase plasminogen activator in human dental pulp cells.
abstract: Plasminogen activator (PA) is the enzyme responsible for converting plasminogen to its active form, plasmin, which is involved in various physiological and pathological phenomena. PA exists in two forms: urokinase-type PA (uPA) and tissue-type PA (tPA). Here we investigated the effect of the inflammatory cytokine tumor necrosis factor α (TNF-α) on PA production and secretion in human dental pulp cells. When the cells were stimulated with TNF-α (10 ng/mL), PA activity in the medium clearly increased in a time-dependent manner, and this activity was reduced after immunoprecipitation with anti-uPA antibody, but not with anti-tPA antibody. In TNF-α-stimulated cells, the expression of uPA mRNA was enhanced, but was lower than that of tPA mRNA. The expression of uPA mRNA and PA secretion stimulated by TNF-α were reduced by the tyrosine kinase inhibitors herbimycin A and genistein, and by the NFκB inhibitor pyrrolidine dithiocarbamate, but were augmented by the tyrosine phosphatase inhibitor sodium orthovanadate. In the presence of another inflammatory cytokine, interleukin 1β (IL-1β, 100 pg/mL), TNF-α-stimulated expression of uPA mRNA and secretion of uPA were enhanced. These observations suggest that TNF-α stimulates uPA production and secretion, and that this effect is regulated via activation of NFκB and tyrosine phosphorylation, apparently in conjunction with IL-1β, during inflammation in human dental pulp.
authors.affiliation: Laboratory of Veterinary Biochemistry, Nihon University College of Bioresource Sciences, Fujisawa, Japan. narita.takanori@nihon-u.ac.jp
authors.forename: Takanori
authors.initials: T
authors.lastname: Narita
authors.forename: Koichiro
authors.initials: K
authors.lastname: Muromachi
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: Hideki
authors.initials: H
authors.lastname: Hashizume
mesh_terms: D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D016328:NF-kappa B / Q000494:pharmacology*; D010766:Phosphorylation; D010960:Plasminogen Activators / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; D017828:Rifabutin; C020972:pyrrolidine dithiocarbamic acid; D014638:Vanadates; D014443:Tyrosine; C020754:herbimycin; D019833:Genistein; D010960:Plasminogen Activators