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 plasminogen activator inhibitor‐2 (PAI‐2) in murine macrophages. PAI‐2 mRNA was inducible by bacterial lipopolysaccharide (LPS) in primary cells and macrophage‐like cell lines. Evidence is presented for a role for autocrine factors, including cyclooxygenase products but not the cytokines tumor necrosis factor α or interferon‐β (IFN‐β). 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 response, and sensitivity to co‐stimulation with IFN‐γ. Induction of PAI‐2 mRNA in subclones of the cell line RAW 264 was not uniform, reflecting heterogeneous 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.