IL-1β Acts in Synergy with Endogenous IL-1β in A375-S2 Human Melanoma Cell Apoptosis Through Mitochondrial Pathway

Abstract

Interleukin-1β (IL-1β) is a pivotal proinflammatory cytokine. To investigate the mechanism of IL-1β-induced cell death in human malignant melanoma A375-S2 cells, MTT assay, photomicroscopical observation, DNA agarose gel electrophoresis, radioimmunoassay and Western blot analysis were carried out. IL-1β did not only induce nuclear condensation and DNA fragmentation, but also increased degradation of two substrates of caspase-3, poly ADP-ribose polymerase (PARP) and inhibitor of caspase-activated DNase (ICAD). Simultaneously, release of precursor of IL-1β (pro-IL-1β) and endogenous IL-1β production were involved in the apoptotic process. IL-1β enhanced the ratio of Bax/Bcl-2 and Bax/Bcl-xL expression and up-regulated apoptosis inducing factor (AIF) expression, which required the activation of downstream caspases. These results suggest that IL-1β induces endogenous IL-1β production, enhances cleavage of caspase downstream substrates and promotes mitochondria mediated apoptosis in A375-S2 cells.