Wang Che, Wang Min-wei, Tashiro Shin-ichi, Onodera Satoshi, Ikejima Takashi
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, China.
J Korean Med Sci. 2005 Aug;20(4):555-61. doi: 10.3346/jkms.2005.20.4.555.
Interleukin-1beta (IL-1beta) is a pivotal proinflammatory cytokine. To investigate the mechanism of IL-1beta-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-1beta 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-1beta (pro-IL-1beta) and endogenous IL-1beta production were involved in the apoptotic process. IL-1beta 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-1beta induces endogenous IL-1beta production, enhances cleavage of caspase downstream substrates and promotes mitochondria mediated apoptosis in A375-S2 cells.
白细胞介素-1β（IL-1β）是一种关键的促炎细胞因子。为了研究IL-1β诱导人恶性黑色素瘤A375-S2细胞死亡的机制，进行了MTT法、显微镜观察、DNA琼脂糖凝胶电泳、放射免疫测定和蛋白质印迹分析。IL-1β不仅诱导细胞核浓缩和DNA片段化，还增加了半胱天冬酶-3的两种底物聚ADP核糖聚合酶（PARP）和半胱天冬酶激活的脱氧核糖核酸酶抑制剂（ICAD）的降解。同时，IL-1β前体（pro-IL-1β）的释放和内源性IL-1β的产生参与了凋亡过程。IL-1β提高了Bax/Bcl-2和Bax/Bcl-xL的表达比例，并上调了凋亡诱导因子（AIF）的表达，这需要下游半胱天冬酶的激活。这些结果表明，IL-1β诱导内源性IL-1β的产生，增强半胱天冬酶下游底物的切割，并促进A375-S2细胞中线粒体介导的凋亡。
