Balance between autocrine interleukin-1b and caspases defines life versus death of polymorphonuclear cells.

NCBINCBI Logo Skip to main content Skip to navigation Resources How To About NCBI Accesskeys Sign in to NCBI PubMed US National Library of Medicine National Institutes of Health Search termSearch database Clear input Advanced Help Result Filters Display Settings: Abstract Send to: Eur Cytokine Netw. 2001 Mar;12(1):177-86. Balance between autocrine interleukin-1beta and caspases defines life versus death of polymorphonuclear cells. Bossù P, del Grosso E, Cesaroni MP, Maurizi G, Balestro N, Stoppacciaro A, del Giudice E, Ruggiero P, Boraschi D. Source Research Center Dompé S.p.A., Via Campo di Pile, I-67100 L'Aquila, Italy. bossu.paola@dompe.it Abstract The role of endogenous IL-1beta in regulating spontaneous and Fas-triggered apoptosis of human PMN has been studied in relation to the activity of the IL-1beta-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-1beta, caspase-1- and caspase-3-like enzymes. Endogenous IL-1beta protects PMN from apoptosis, since inhibition of either IL-1beta 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-1beta, whereas other molecules are responsible of driving apoptosis. Upon Fas triggering, PMN apoptosis is greatly accelerated, in correlation with increased caspase activity, whereas IL-1beta production is not augmented. Inhibition of IL-1beta 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-1beta, as in spontaneous apoptosis, and it can also exert pro-apoptotic activity which counterbalances the protective effect and allows accelerated apoptosis.