Tumor necrosis factor α stimulates expression and secretion of urokinase plasminogen activator in human dental pulp cells

• Published in: Journal of Oral Science 2012, Vol.54(4), pp.329-336
• Main Authors: Narita, Takanori, Muromachi, Koichiro, Kamio, Naoto, Nakao, Sumi, Matsushima, Kiyoshi, Hashizume, Hideki
• Format: Article
• Language: English
• Subjects: Cells, Cultured; dental pulp; Dental Pulp - cytology; Dental Pulp - drug effects; Dental Pulp - metabolism; Dentistry; Genistein - pharmacology; Humans; Interleukin-1 - pharmacology; NF-kappa B - pharmacology; NFκB; Phosphorylation; Plasminogen Activators - metabolism; Plasminogen Activators - secretion; Pyrrolidines - pharmacology; Rifabutin - analogs & derivatives; Rifabutin - pharmacology; Thiocarbamates - pharmacology; TNF-α; Tumor Necrosis Factor-alpha - pharmacology; Tyrosine - metabolism; tyrosine phosphorylation; uPA; Vanadates - pharmacology
• ISSN: 1343-4934; 1880-4926
• DOI: 10.2334/josnusd.54.329

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. (J Oral Sci 54, 329-336, 2012)