Tamura T, Ueda S, Yoshida M, Matsuzaki M, Mohri H, Okubo T
First Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Biochem Biophys Res Commun. 1996 Dec 4;229(1):21-6. doi: 10.1006/bbrc.1996.1752.
The roles of interferons (IFNs) in apoptosis are not fully understood. In this study we show that in the U937 monoblastic leukemia cell line, pretreatment with IFN-gamma enhanced sensitivity to apoptosis triggered by gamma-irradiation or antitumor agents (etoposide or adriamycin), as well as by anti-Fas antibody. In addition, IFN-gamma caused an increased expression of the interleukin-1 beta-converting enzyme (Ice) gene, following strong induction of the interferon regulatory factor-1 (IRF-1) gene, the product of which is a transcriptional activator of the Ice gene. An inhibitor of ICE/Ced-3 family proteases, Z-Asp-CH2-DCB, blocked apoptosis in control cells as well as in IFN-gamma-pretreated cells. These results suggest that enhanced susceptibility of IFN-gamma-pretreated cells to apoptosis is mediated through the induction of Ice by IRF-1. This pathway is not affected by interleukin-1 beta (IL-1 beta) since neutralizing antibody against IL-1 beta failed to suppress the IFN-gamma-mediated enhancement of cell death, and IL-1 beta itself did not mimic the effect of IFN-gamma.
干扰素（IFN）在细胞凋亡中的作用尚未完全明确。在本研究中，我们发现，在U937单核细胞白血病细胞系中，用γ干扰素预处理可增强细胞对由γ射线照射、抗肿瘤药物（依托泊苷或阿霉素）以及抗Fas抗体引发的细胞凋亡的敏感性。此外，γ干扰素在强烈诱导干扰素调节因子-1（IRF-1）基因后，会导致白细胞介素-1β转换酶（Ice）基因表达增加，IRF-1基因的产物是Ice基因的转录激活因子。ICE/Ced-3家族蛋白酶的抑制剂Z-Asp-CH2-DCB可阻断对照细胞以及经γ干扰素预处理细胞的凋亡。这些结果表明，经γ干扰素预处理的细胞对细胞凋亡敏感性增强是由IRF-1诱导Ice介导的。该途径不受白细胞介素-1β（IL-1β）影响，因为抗IL-1β中和抗体未能抑制γ干扰素介导的细胞死亡增强，且IL-1β本身也无法模拟γ干扰素的作用。
