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

人牙髓细胞中细胞因子相关纤溶酶原激活剂的活性和调节

• 批准号: 17592001
• 负责人: HASHIZUME Hideki
• 金额: $ 2.24万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17592001/
• 关键词: cytokine; plasminogen avtivator; urokinase; NF-κB; IL-1β; TNF-α; uPA; チロシンのリン酸化

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.

纤溶酶原激活剂（PA）是将纤溶酶原转化为活性形式的酶，参与多种生理病理现象。该转化由两种类型的纤溶酶原激活剂（PA）催化，尿激酶型PA和组织型PA（tPA）。本研究观察了炎症因子IL-1 β和TNF-α对人牙髓细胞分泌PA的影响。IL-1β和TNF-α刺激细胞后，培养液中PA活性明显升高，并呈时间和剂量依赖性。用抗uPA抗体免疫沉淀后，培养基中的PA活性降低，并通过Western印迹法在免疫沉淀组分中检测到uPA蛋白。抗tPA抗体未显示出这些观察结果。在IL-1β和TNF-α刺激的细胞中，uPA mRNA表达增强，但tPA mRNA表达减少。酪氨酸激酶抑制剂除莠霉素A、染料木素和NFκB抑制剂吡咯烷二硫代氨基甲酸盐可降低IL-1β和TNF-α刺激的uPA mRNA表达和PA活性，酪氨酸磷酸酶抑制剂原钒酸钠可增强uPA mRNA表达和PA活性。提示IL-1β和TNF-α通过激活NFκB和酪氨酸磷酸化促进uPA的产生和分泌，uPA/纤溶酶系统可能参与了人牙髓的炎症反应。