Contribution of IL-6 to the antiproliferative effect of IL-1 and tumor necrosis factor on tumor cell lines.
Contribution of IL-6 to the antiproliferative effect of IL-1 and tumor necrosis factor on tumor cell lines.
复制标题
IL-6 对 IL-1 和肿瘤坏死因子对肿瘤细胞系的抗增殖作用的贡献。
作者：
Y. Morinaga;H. Suzuki;F. Takatsuki;Y. Akiyama;T. Taniyama;K. Matsushima;K. Onozaki
使用IL-1敏感的细胞系研究IL-6在IL-1对肿瘤细胞系的抗增殖作用中的作用。人重组IL-1 α和IL-6均抑制IL-1敏感的克隆人黑色素瘤细胞系（A375-C6）的生长。然而，IL-1具有比IL-6更大的最大生长抑制活性。经ELISA测定，用IL-1处理的肿瘤细胞的条件培养基含有IL-6。北方印迹分析显示IL-1处理的细胞中IL-6 mRNA表达增加。此外，抗人IL-6的抗体中和了IL-1约50%的抗增殖作用。A375细胞的IL-1抗性克隆（A375-C5）的生长不能显示出表达任何可检测的IL-1 R，其被IL-6抑制至与A375-C6细胞相同的程度。A375-C5细胞系在用IL-1刺激后不产生IL-6或增加IL-6 mRNA。这些结果表明，IL-6介导的IL-1对A375-C6细胞的抗增殖作用的一部分，作为一种自分泌抗增殖因子。IL-1还抑制恶性人乳腺细胞系（MDA-MB-415）的生长。IL-6在该细胞系中仅表现出轻微的生长抑制。在该细胞系中，IL-1既不诱导IL-6产生，也不诱导IL-6 mRNA表达。抗IL-6抗体不能中和IL-1的抗增殖作用。因此，对于MDA-MB-415细胞，IL-6似乎不参与IL-1的抗增殖作用。这些结果表明，IL-1的抗增殖作用涉及至少两个途径，一个IL-6依赖性和另一个IL-6非依赖性。还检查了IL-6对TNF的抗增殖作用的贡献。IL-6似乎没有发挥作用，在这些细胞系中的TNF的抗增殖作用。
The role of IL-6 in the antiproliferative effect of IL-1 for tumor cell lines was investigated using IL-1-sensitive cell lines. Human recombinant IL-1 alpha and IL-6 both inhibited the growth of an IL-1-sensitive cloned human melanoma cell line (A375-C6). However, IL-1 has greater maximum growth inhibitory activity than IL-6. Conditioned medium of the tumor cells that were treated with IL-1 contained IL-6 as determined by ELISA. Northern blot analysis revealed that IL-6 mRNA expression increased in IL-1-treated cells. In addition, antibody against human IL-6 neutralized about 50% of the antiproliferative effect of IL-1. The growth of an IL-1-resistant clone of A375 cells (A375-C5), which cannot be shown to express any detectable IL-1R, was inhibited by IL-6 to the same degree as A375-C6 cells. The A375-C5 cell line did not produce IL-6 or increase IL-6 mRNA after stimulation with IL-1. These results indicate that IL-6 mediates in part the antiproliferative effect of IL-1 on A375-C6 cells by acting as an autocrine antiproliferative factor. IL-1 also inhibited the growth of a malignant human mammary cell line (MDA-MB-415). IL-6 exhibited only slight growth inhibition in this cell line. Neither IL-6 production nor IL-6 mRNA expression was induced in this cell line by IL-1. Antibody against IL-6 did not neutralize the antiproliferative effect of IL-1. Therefore, for MDA-MB-415 cells IL-6 appeared not to be involved in the antiproliferative effect of IL-1. These results indicate that the antiproliferative effect of IL-1 involves at least two pathways, one IL-6 dependent and another IL-6 independent. The contribution of IL-6 to the antiproliferative effect of TNF was also examined. IL-6 appeared not to play a role in the antiproliferative effect of TNF in these cell lines.