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.
|Number of pages||10|
|Journal||European Cytokine Network|
|Publication status||Published - 2001|
- Polymorphonuclear leukocytes
ASJC Scopus subject areas
- Cell Biology