Balance between autocrine interleukin-1β and caspases defines life versus death of polymorphonuclear leukocytes

P. Bossù, E. Del Grosso, M. P. Cesaroni, M. Giovanni, N. Balestro, A. Stoppacciaro, E. Del Giudice, P. Ruggiero, D. Boraschi

Research output: Contribution to journalArticlepeer-review

Abstract

The role of endogenous IL-1β in regulating spontaneous and Fas-triggered apoptosis of human PMN has been studied in relation to the activity of the IL-1β-generating enzyme ICE (caspase-1), an enzyme also involved in the mechanism of cell death. Upon in vitro culture, PMN undergo spontaneous apoptosis and express increasing levels of IL-1β, caspase-1- and caspase-3-like enzymes. Endogenous IL-1β protects PMN from apoptosis, since inhibition of either IL-1β or caspase-1 activity can accelerate PMN apoptotic death. Thus, in spontaneous PMN apoptosis caspase-1 essentially plays an anti-apoptotic role by inducing maturation of protective IL-1β, whereas other molecules are responsible of driving apoptosis. Upon Fas triggering, PMN apoptosis is greatly accelerated, in correlation with increased caspase activity, whereas IL-1β production is not augmented. Inhibition of IL-1β activity can increase Fas-induced apoptosis, whereas caspase-1 inhibitors are without significant effect. It is hypothesized that in Fas-induced PMN apoptosis caspase-1 has a double role: it can protect from apoptosis through generation of protective IL-1β, as in spontaneous apoptosis, and it can also exert pro-apoptotic activity which counterbalances the protective effect and allows accelerated apoptosis.

Original languageEnglish
Pages (from-to)177-186
Number of pages10
JournalEuropean Cytokine Network
Volume12
Issue number1
Publication statusPublished - 2001

Keywords

  • Apoptosis
  • Caspases
  • ICE
  • Interleukin-1
  • Polymorphonuclear leukocytes

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

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