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 alpha or interferon-beta (IFN-beta). 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-gamma. 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.
Department of Biochemistry, Centre for Molecular and Cellular Biology, University of Queensland, Australia.
E O
EO
Costelloe
K J
KJ
Stacey
T M
TM
Antalis
D A
DA
Hume
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism* / Q000494:pharmacology; D015152:Blotting, Northern; D002460:Cell Line; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics*; D012333:RNA, Messenger
D001427:Bacterial Toxins; D008070:Lipopolysaccharides; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger