Niikura T, Hirata R, Weil S C
Department of Pathology, Cell Biology, and Medicine, Thomas Jefferson University, Philadelphia, PA 19107-5099, USA.
Blood Cells Mol Dis. 1997 Dec;23(3):337-49. doi: 10.1006/bcmd.1997.0151.
The acute promyelocytic leukemia cell line, NB4, can be induced to differentiate to mature granulocytes by retinoic acid treatment. A novel retinoic acid-inducible cDNA clone, designated RI58, was isolated from a cDNA library constructed from retinoic acid-treated NB4 cells by differential hybridization. RI58 cDNA encodes a protein of 58kDa which has a similarity in its amino acids sequence to interferon (IFN)-inducible proteins. In addition, RI58 was induced by recombinant human IFN-alpha (rhIFN-alpha) in NB4 cells. RI58 was detectable within 4 hours post-stimulation with rhIFN-alpha, while it took as long as 1day after retinoic acid stimulation. Culture supernatant from retinoic acid-treated NB4 cells also induced RI58 expression similarly as rhIFN-alpha. This activity in culture supernatant was inhibited by anti-leukocyte IFN antiserum which showed specific reactivity to rhIFN-alpha. These results indicate that RI58 is induced by retinoic acid stimulation through autocrinally secreted IFN-alpha from NB4 cells. In the retinoic acid-treated NB4 cells, the expression of RI58 was increased along the process of differentiation. On the other hand, it was expressed constitutively in untreated non-hematopoietic cell lines and mature hematopoietic cell lines.
急性早幼粒细胞白血病细胞系NB4可通过维甲酸处理诱导分化为成熟粒细胞。通过差异杂交从经维甲酸处理的NB4细胞构建的cDNA文库中分离出一个新的维甲酸诱导型cDNA克隆,命名为RI58。RI58 cDNA编码一种58kDa的蛋白质,其氨基酸序列与干扰素(IFN)诱导蛋白相似。此外,RI58在NB4细胞中可被重组人IFN-α(rhIFN-α)诱导。用rhIFN-α刺激后4小时内可检测到RI58,而维甲酸刺激后则需要长达1天的时间。经维甲酸处理的NB4细胞的培养上清液也能像rhIFN-α一样诱导RI58表达。培养上清液中的这种活性被对rhIFN-α具有特异性反应的抗白细胞IFN抗血清所抑制。这些结果表明,RI58是通过NB4细胞自分泌的IFN-α经维甲酸刺激诱导产生的。在经维甲酸处理的NB4细胞中,RI58的表达随着分化过程而增加。另一方面,它在未处理的非造血细胞系和成熟造血细胞系中组成性表达。