Furukawa Y, Kikuchi J, Terui Y, Kitagawa S, Ohta M, Miura Y, Saito M
Division of Hemopoiesis, Jichi Medical School, Tochigi.
Jpn J Cancer Res. 1995 Feb;86(2):208-16. doi: 10.1111/j.1349-7006.1995.tb03041.x.
Normal human monocytes were isolated in a nascent state by centrifugal elutriation and used for the study of interleukin-1 (IL-1) and interleukin-1 receptor antagonist (IL-1ra) expression. Neither IL-1 beta nor IL-1ra mRNA was present in monocytes just after the isolation, but they were induced simultaneously in response to various stimulants. In contrast, only IL-1 beta mRNA was expressed in monocytic leukemia cell line JOSK-1, while little or no IL-1ra mRNA was detected even after stimulation. Dominant expression of IL-1 beta over IL-1ra was also observed in fresh leukemia cells including monocytic leukemias, i.e., IL-1 beta mRNA was constitutively expressed in 26 out of 36 cases (72.2%), whereas IL-1ra mRNA was present only in 8 cases (22.2%). The signal intensity of IL-1 beta mRNA was stronger than that of IL-1ra even in IL-1ra-positive cases. Apoptotic cell death of monocytes was significantly inhibited by IL-1 beta, and it was enhanced by IL-1ra. In fresh leukemia cells, 3H-thymidine uptake was generally higher in IL-1-producing cases than in IL-1ra-producing cases, and was increased by the addition of IL-1 beta in all cases tested. Cell proliferation was inhibited by either IL-1ra or anti-IL-1 beta antibody in IL-1-producing cases, while it was enhanced by anti-IL-1ra antibody in IL-1ra-producing cases. These results suggest that the balance between IL-1 and IL-1ra is necessary for homeostasis of the mononuclear phagocytosis system. The imbalance between these two counter-acting cytokines might contribute to the altered growth and accumulation of leukemic cells.
通过离心淘析法分离出处于新生状态的正常人单核细胞，并用于研究白细胞介素-1（IL-1）和白细胞介素-1受体拮抗剂（IL-1ra）的表达。刚分离后的单核细胞中既不存在IL-1β也不存在IL-1ra mRNA，但它们在受到各种刺激后同时被诱导表达。相比之下，单核细胞白血病细胞系JOSK-1中仅表达IL-1β mRNA，即使在刺激后也几乎检测不到IL-1ra mRNA。在包括单核细胞白血病在内的新鲜白血病细胞中也观察到IL-1β相对于IL-1ra的优势表达，即36例中有26例（72.2%）IL-1β mRNA组成性表达，而IL-1ra mRNA仅在8例（22.2%）中存在。即使在IL-1ra阳性病例中，IL-1β mRNA的信号强度也强于IL-1ra。IL-1β可显著抑制单核细胞的凋亡性细胞死亡，而IL-1ra则增强这种作用。在新鲜白血病细胞中，产生IL-1的病例中3H-胸腺嘧啶核苷摄取通常高于产生IL-1ra的病例，并且在所有测试病例中添加IL-1β后摄取增加。在产生IL-1的病例中，IL-1ra或抗IL-1β抗体均可抑制细胞增殖，而在产生IL-1ra的病例中，抗IL-1ra抗体则增强细胞增殖。这些结果表明，IL-1和IL-1ra之间的平衡对于单核吞噬系统的稳态是必要的。这两种相互拮抗的细胞因子之间的失衡可能导致白血病细胞生长和积聚的改变。
