Koyasu S, Miyajima A, Arai K, Okajima F, Ui M, Yahara I
Department of Cell Biology, Tokyo Metropolitan Institute of Medical Science.
Cell Struct Funct. 1989 Aug;14(4):459-71. doi: 10.1247/csf.14.459.
The stimulatory effects of lymphokines, interleukin 3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 4 (IL-4), and the inhibitory effects of transforming growth factor beta (TGF-beta) and the pertussis toxin, islet activating protein (LAP), on multi-factor-dependent myeloid cell lines were examined. The effects of IL-3 on a mast cell progenitor clone, IC2 were indistinguishable from those of GM-CSF with respect to their concentration-response curves for induction of DNA synthesis and capability to maintain cell growth for many months. IL-4 acts differently on IC2 cells: the maximum level of DNA synthesis induced by IL-4 is always lower than that induced by IL-3 or GM-CSF and IL-4-induced proliferation is transient. IL-4, however, synergistically induced DNA synthesis of IC2 cells with limiting concentrations of IL-3 or GM-CSF. When IC2 cells were cultured with saturating concentrations of IL-3, GM-CSF or a combination of both, the doubling time was 25 +/- 1 h, whereas it decreased to 17 +/- 1 h when IL-4 was further added to the cultures. IAP reduced the DNA synthesis of IC2 cells induced by the above three growth factors. The doubling time of IC2 cells was 30 +/- 2 h when IC2 cells were cultured with sufficient concentrations of IL-3 in the presence of IAP. Cell cycle analysis revealed that the fraction of cells in Gl was decreased by IL-4 but was increased by IAP. TGF-beta also reduced IL-3-dependent DNA synthesis and increased the fraction of cells in Gl. The inhibitory effect on IL-3-dependent growth of IC2 cells was not increased when these cells were exposed simultaneously to TGF-beta and IAP. The results suggest that IL-3 and GM-CSF stimulate the growth of IC2 cells through similar pathways and that IL-4 augments the action of IL-3 or GM-CSF by decreasing the Gl period. It is also suggested that IAP and TGF-beta retard the growth of IC2 cells by increasing the fraction of cells in GI.
研究了淋巴因子、白细胞介素3（IL-3）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素4（IL-4）的刺激作用，以及转化生长因子β（TGF-β）和百日咳毒素、胰岛激活蛋白（LAP）对多因子依赖性髓系细胞系的抑制作用。IL-3对肥大细胞祖细胞克隆IC2的作用，在诱导DNA合成的浓度-反应曲线和维持细胞生长数月的能力方面，与GM-CSF的作用难以区分。IL-4对IC2细胞的作用不同：IL-4诱导的DNA合成的最大水平总是低于IL-3或GM-CSF诱导的水平，且IL-4诱导的增殖是短暂的。然而，IL-4与极限浓度的IL-3或GM-CSF协同诱导IC2细胞的DNA合成。当IC2细胞用饱和浓度的IL-3、GM-CSF或两者的组合培养时，倍增时间为25±1小时，而当向培养物中进一步添加IL-4时，倍增时间降至17±1小时。IAP降低了上述三种生长因子诱导的IC2细胞的DNA合成。当IC2细胞在IAP存在下用足够浓度的IL-3培养时，IC2细胞的倍增时间为30±2小时。细胞周期分析显示，G1期细胞比例因IL-4而降低，但因IAP而增加。TGF-β也降低了IL-3依赖性DNA合成，并增加了G1期细胞比例。当这些细胞同时暴露于TGF-β和IAP时，对IC2细胞IL-3依赖性生长的抑制作用并未增强。结果表明，IL-3和GM-CSF通过相似途径刺激IC2细胞生长，且IL-4通过缩短G1期增强IL-3或GM-CSF的作用。还表明，IAP和TGF-β通过增加G1期细胞比例来延缓IC2细胞生长。
