Regulation of plasminogen activator inhibitor-1 and urokinase by hyaluronan fragments in mouse macrophages.
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.
Horton
M R
MR
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Olman
M A
MA
Bao
C
C
White
K E
KE
Choi
A M
AM
Chin
B Y
BY
Noble
P W
PW
Lowenstein
C J
CJ
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006820:Hyaluronic Acid / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D000584:Amiloride; D006820:Hyaluronic Acid; D014568:Urokinase-Type Plasminogen Activator