University Of Tasmania

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Plasminogen activator inhibitor type 2 inhibits tumour necrosis factor alpha-induced apoptosis. Evidence for an alternate biological function

journal contribution
posted on 2023-05-16, 16:50 authored by Joanne DickinsonJoanne Dickinson, Bates, EJ, Ferrante, A, Antalis, TM
Plasminogen activator inhibitor type 2 (pAI-2) is a serine proteinase inhibitor or serpin that is a major product of macrophages in response to endotoxin and inflammatory cytokines. We have explored the role of PAI-2 in apoptotic cell death initiated by tumor necrosis factor a (TNF). HeLa cells stably transfected with PAI-2 cDNA were protected from TNF-induced apoptosis, whereas cells transfected with antisense PAI-2 cDNA, a control gene, or the plasmid vector alone remained susceptible. The level of PAI-2 expressed by different HeLa cell clones was inversely correlated with their sensitivity to TNF. Loss of TNF sensitivity was not a result of loss of TNF receptor binding. In contrast, PAI-2 expression did not confer protection against apoptosis induced by ultraviolet or ionizing radiation. The serine proteinase urokinase-type plasminogen activator was not demonstrated to be the target of pAI-2 action. The P 1 -Arg amine acid residue of PAI-2 was determined to be required for protection, because cells expressing PAI-2 with an Ala in this position were not protected from TNF-mediated cell death. The results suggest that intracellular PAI-2 might he an important factor in regulating cell death in TNF-mediated inflammatory processes through inhibition of a proteinase involved in TNF-induced apoptosis.


Publication title

Journal of Biological Chemistry










Menzies Institute for Medical Research


American Society for Biochemistry and Molecular Biology Inc

Place of publication

United States

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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