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首页> 外文期刊>Biomedical Research >IL-1β stimulates urokinase-type plasminogen activator expression and secretion in human dental pulp cells
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IL-1β stimulates urokinase-type plasminogen activator expression and secretion in human dental pulp cells

机译：IL-1β刺激人牙髓细胞中尿激酶型纤溶酶原激活物的表达和分泌

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摘要

Plasminogen activator (PA) is the enzyme that converts plasminogen to its active form, plasmin, which is 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). We investigated the effect of the inflammatory cytokine interleukin-1β (IL-1β) on PA secretion in human dental pulp cells. When the cells were stimulated by IL-1β, PA activity in the medium was clearly increased in a time- and dose-dependent manner. This PA activity in the medium was reduced after immunoprecipitation with anti-uPA antibody, and uPA protein was detected in the immunoprecipitated fraction by Western blotting. However, no such effect was observed with anti-tPA antibody. In the IL-1β-stimulated cells, expression of uPA mRNA was enhanced whereas expression of tPA mRNA was less. The IL-1β-stimulated uPA mRNA expression and PA activities in the cell lysate and medium were reduced by the tyrosine kinase inhibitors herbimycin A and genistein, and by the NFκB inhibitor pyrolidinedithiocarbamate, and were augmented by the tyrosine phosphatase inhibitor sodium orthovanadate. These observations suggest that IL-1β stimulates uPA production via activation of NFκB and tyrosine phosphorylation, and also secretion of the enzyme, and that the uPA/plasmin system appears to be involved in inflammation in human dental pulp.
机译：纤溶酶原激活剂（PA）是将纤溶酶原转化为其活性形式的纤溶酶的酶，纤溶酶参与各种生理和病理现象。两种类型的PA催化转化，尿激酶型PA（uPA）和组织型PA（tPA）。我们调查了炎性细胞因子白介素1β（IL-1β）对人牙髓细胞中PA分泌的影响。当细胞被IL-1β刺激时，培养基中的PA活性以时间和剂量依赖性方式明显增加。用抗uPA抗体免疫沉淀后，培养基中的PA活性降低，并且通过Western印迹在免疫沉淀级分中检测到uPA蛋白。然而，用抗tPA抗体没有观察到这样的作用。在IL-1β刺激的细胞中，uPA mRNA的表达增强，而tPA mRNA的表达较少。酪氨酸激酶抑制剂除草霉素A和染料木黄酮，以及NFκB抑制剂吡咯烷二硫代氨基甲酸酯可降低IL-1β刺激的uPA mRNA在细胞裂解液和培养基中的表达，并被酪氨酸磷酸酶抑制剂原钒酸钠增强。这些观察结果表明，IL-1β通过激活NFκB和酪氨酸磷酸化以及酶的分泌来刺激uPA的产生，并且uPA /纤溶酶系统似乎与人类牙髓的炎症有关。

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