Regulation of plasminogen activator inhibitor-1 and urokinase by hyaluronan fragments in mouse macrophages
Regulation of plasminogen activator inhibitor-1 and urokinase by hyaluronan fragments in mouse macrophages
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DOI：
10.1152/ajplung.2000.279.4.l707
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发表时间：
2000-10-01
影响因子：
4.9
通讯作者：
Lowenstein, CJ
中科院分区：
文献类型：
--
作者：
Horton, MR;Olman, MA;Lowenstein, CJ
肺部炎症和纤维化的特征在于细胞外基质的周转和产生增加以及肺纤维蛋白溶解活性受损。尽管细胞外基质组分透明质酸的片段诱导巨噬细胞产生炎症介质，但透明质酸对纤溶介质纤溶酶原激活物抑制剂（派）-1和尿激酶型纤溶酶原激活物（uPA）的影响尚不清楚。这项研究表明，透明质酸片段增加稳态mRNA，蛋白质和抑制活性的派-1，以及减少基线水平的uPA mRNA和抑制uPA活性在肺泡巨噬细胞系。Hybryonan片段在基因转录水平上改变巨噬细胞派-1和uPA的表达。同样，透明质酸片段增加派-1和减少uPA mRNA水平在新鲜分离的炎症肺泡巨噬细胞从博来霉素治疗的大鼠。这些数据表明，透明质酸片段影响肺泡巨噬细胞表达派-1和uPA，并可能是一种机制，调节纤溶活性在肺部炎症。
Pulmonary inflammation and fibrosis are characterized by increased turnover and production of the extracellular matrix as well as an impairment of lung fibrinolytic activity. Although fragments of the extracellular matrix component hyaluronan induce macrophage production of inflammatory mediators, the effect of hyaluronan on the fibrinolytic mediators plasminogen activator inhibitor (PAI)-1 and urokinase-type plasminogen activator (uPA) is unknown. This study demonstrates that hyaluronan fragments augment steady-state mRNA, protein, and inhibitory activity of PAI-1 as well as diminish the baseline levels of uPA mRNA and inhibit uPA activity in an alveolar macrophage cell line. Hyaluronan fragments alter macrophage expression of PAI-1 and uPA at the level of gene transcription. Similarly, hyaluronan fragments augment PAI-1 and diminish uPA mRNA levels in freshly isolated inflammatory alveolar macrophages from bleomycin-treated rats. These data suggest that hyaluronan fragments influence alveolar macrophage expression of PAI-1 and uPA and may be a mechanism for regulating fibrinolytic activity during lung inflammation.