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-β (≥ 1 ng/ml) and surprisingly down-regulated by LPS (100 ng/ml), particularly in the presence of TGF-β; LPS elevated PAI-2 levels (ELISA) while TGF-β 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-β 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. © 1993 Academic Press. All rights reserved.