Cytokine related plasminogen activator activity and regulation in human dental pulp cells

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17592001
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Conservative dentistry
• Research Institution: Nihon University
• Principal Investigator: HASHIZUME Hideki Nihon University, School of Dentistry at Matsudo, Lecturer (Full-Time), 松戸歯学部, 講師 (10256894)
• Project Period (FY): 2005 – 2006
• Keywords: cytokine / plasminogen avtivator / urokinase / NF-κB

Research Abstract

Plasminogen activator (PA) is the enzyme converting plasminogen to its active form, plasmin involved in various physiological and pathological phenomenon. The conversion is catalysed by two types of plasminogen activator (PA), urokinase-type PA and tissue-type PA (tPA). We investigated effect of the inflammatory cytokin IL-lβ and TNF-a on PA secretion in human dental pulp cells. When the cells were stimulated by IL-1β and TNF-a, PA activity in the medium was clearly increased in a time-and dose-dependent manner. The PA activity in the medium was reduced after immunoprecipitation using anti-uPA antibody, and uPA protein was detected in the immunoprecipitated fraction by Western blotting. Anti-tPA antibody failed to show such observations. In the IL-1β and TNF-a-stimulated cells, uPA mRNA expression was enhanced but less tPA mRNA. The IL-1β and TNF-a-stimulated uPA mRNA expresson and PA activities in cell lysate and medium were reduced by herbimycin A and genistein, tyrosin kinase inhibitors, and pyrolidinedithiocarbamate, an NFκB inhibitor, and were augmented by the tyrosine phosphatase inhibitor sodium orthovanadate. These observations suggest that IL-1β and TNF-a stimulates uPA production via NFκB and tyrosine phosphorylation activation and the enzyme secretion, and uPA/plasmin system appears to be involved in inflammation in human dental pulp.