Balance between autocrine interleukin-1beta and caspases defines life versus death of polymorphonuclear cells.
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.
Research Center Dompé S.p.A., Via Campo di Pile, I-67100 L'Aquila, Italy. bossu.paola@dompe.it
P
P
Bossù
E
E
del Grosso
M P
MP
Cesaroni
G
G
Maurizi
N
N
Balestro
A
A
Stoppacciaro
E
E
del Giudice
P
P
Ruggiero
D
D
Boraschi
D000328:Adult; D017209:Apoptosis / Q000502:physiology; D020170:Caspase 1 / Q000378:metabolism*; D061945:Caspase Inhibitors; D002470:Cell Survival; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology*; D019014:fas Receptor / Q000502:physiology
D061945:Caspase Inhibitors; D007375:Interleukin-1; D019014:fas Receptor; D020170:Caspase 1