Regulation of plasminogen activator inhibitor-1 levels in human monocytes.
The regulation of PAI-1 synthesis by elutriation-purified human monocytes was studied in vitro and compared to that for PAI-2. PAI-1 formation, as measured by ELISA, was upregulated by TGF-beta (> or = 1 ng/ml) and surprisingly down-regulated by LPS (100 ng/ml), particularly in the presence of TGF-beta; LPS elevated PAI-2 levels (ELISA) while TGF-beta reduced its basal levels and those in LPS-treated cultures. Concomitant changes in mRNA expression occurred. The glucocorticoid dexamethasone (10(-7) M) elevated PAI-1 and acted in concert with TGF-beta in this regard at both the antigen and mRNA levels; interleukin-4 (IL-4) (250 pM) failed to mimic the steroid in its regulation of PAI-1 formation. Since monocyte/macrophage PA activity is likely to be important in tissue remodeling and cell migration at sites of inflammation and in fibrinolysis, it is proposed from these studies that PAI-1, as well as the usually considered PAI-2, may be involved in the negative control of PA activity in this cell type. The synthesis of each PAI appears to be independently regulated.
Hamilton
J A
JA
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Australia.
Whitty
G A
GA
Wojta
J
J
Gallichio
M
M
McGrath
K
K
Ianches
G
G
D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000097:blood*; D011451:Prostaglandin-Endoperoxide Synthases; D012333:RNA, Messenger / Q000032:analysis; D015291:Transforming Growth Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology
D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D015847:Interleukin-4; D015291:Transforming Growth Factors; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases