Regulation of the plasminogen activator inhibitor-2 (PAI-2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin.

We investigate the regulation of plas- minogen activator inhibitor-2 (PAI-2) in murine macrophages. PAI-2 mRNA was inducible by bacte- rial lipopolysaccharide (LPS) in primary cells and macrophage-like cell lines. Evidence is presented for a role for autocrine factors, including cyclooxy- genase products but not the cytokines tumor necro- sis factor a or interferon-b (IFN-b). PAI-2 mRNA levels generally varied inversely from those of its target, urokinase-type plasminogen activator (uPA), and the macrophage growth factor CSF-1, which induces uPA, inhibited PAI-2 expression in cells treated subsequently with LPS. Expression of PAI-2 was distinct from that of other LPS-inducible genes in terms of induction time course, LPS dose re- sponse, and sensitivity to co-stimulation with IFN-g. Induction of PAI-2 mRNA in subclones of the cell line RAW 264 was not uniform, reflecting heteroge- neous expression in the parent line. The expression pattern of PAI-2 is discussed in terms of a possible role in LPS-induced pathology such as septicemia. J. Leukoc. Biol. 66: 172-182; 1999.