Regulation of plasminogen activator inhibitor-1 and urokinase by hyaluronan fragments in mouse macrophages

Maureen R. Horton, Mitchell A. Olman, Clare Bao, Kimberly E. White, Augustine M. K. Choi, Beek-Yok Chin, Paul W. Noble, Charles J. Lowenstein
2000 American Journal of Physiology - Lung cellular and Molecular Physiology  
ulation of plasminogen activator inhibitor-1 and urokinase by hyaluronan fragments in mouse macrophages. Am J Physiol Lung Cell Mol Physiol 279: L707-L715, 2000.-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
more » ... ronan on the fibrinolytic mediators plasminogen activator inhibitor (PAI)-1 and urokinasetype plasminogen activator (uPA) is unknown. This study demonstrates that hyaluronan fragments augment steadystate 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. extracellular matrix; lung; chronic fibrosis CHRONIC INFLAMMATION AND FIBROSIS are characterized by accumulation of inflammatory cells and mediators, increased turnover and production of the extracellular matrix (ECM), and alterations in the fibrinolytic system (2, 8, 21, 26, 39, 61) . Activated macrophages play an essential role in inflammation through the release of a variety of mediators including reactive oxygen and nitrogen species,
doi:10.1152/ajplung.2000.279.4.l707 pmid:11000131 fatcat:4wuftfjjwjenldxpju4undbqe4