Plasminogen activator inhibitor type 2 inhibits tumor necrosis factor α- induced apoptosis: Evidence for an alternate biological function

Joanne L. Dickinson, Edna J. Bates, Antonio Ferrante, Toni M. Antalis

Research output: Contribution to journalArticle

216 Citations (Scopus)

Abstract

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 P1-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.

LanguageEnglish
Pages27894-27904
Number of pages11
JournalJournal of Biological Chemistry
Volume270
Issue number46
DOIs
Publication statusPublished - 1 Jan 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Dickinson, Joanne L. ; Bates, Edna J. ; Ferrante, Antonio ; Antalis, Toni M. / Plasminogen activator inhibitor type 2 inhibits tumor necrosis factor α- induced apoptosis : Evidence for an alternate biological function. In: Journal of Biological Chemistry. 1995 ; Vol. 270, No. 46. pp. 27894-27904.
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Plasminogen activator inhibitor type 2 inhibits tumor necrosis factor α- induced apoptosis : Evidence for an alternate biological function. / Dickinson, Joanne L.; Bates, Edna J.; Ferrante, Antonio; Antalis, Toni M.

In: Journal of Biological Chemistry, Vol. 270, No. 46, 01.01.1995, p. 27894-27904.

Research output: Contribution to journalArticle

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