Takikawa O, Habara-Ohkubo A, Yoshida R
Department of Cell Biology, Osaka Bioscience Institute, Japan.
J Immunol. 1990 Aug 15;145(4):1246-50.
The depletion of an essential amino acid, tryptophan, caused by induction of indoleamine 2,3-dioxygenase (IDO), has been shown to be a mechanism involving self-defense against inhaled microorganisms and tumor growth. We recently reported that the IDO is dramatically (approximately 50-fold) induced in allografted tumor (3-methylcholanthrene-induced ascites type tumor cells) cells undergoing rejection, and that the enzyme is induced by factor(s) released through the interaction of allografted tumor cells with infiltrating leukocytes. The culture supernatant of infiltrating leukocytes, which were harvested on day 7 after tumor transplantation, induced the highest IDO activity in the tumor cells. The inducer activity was completely neutralized by the addition of antibody to IFN-gamma but not by antibody to IFN-alpha/beta. Approximately 6 U/ml of IFN-gamma was detected by an ELISA assay in the 12-h culture supernatant with 2 x 10(6) leukocytes/ml, and rIFN-gamma at 6 U/ml induced IDO in 3-methylcholanthrene-induced ascites type tumor cells to the same extent as IFN-gamma in the culture supernatant. Moreover, i.p. administration of antibody to IFN-gamma almost completely inhibited the induction of IDO in the allografted tumor cells. These observations indicate that the factor responsible for IDO induction in the allografted tumor cells is IFN-gamma.
由吲哚胺2,3-双加氧酶（IDO）诱导导致的必需氨基酸色氨酸耗竭，已被证明是一种涉及对吸入微生物和肿瘤生长进行自我防御的机制。我们最近报道，在正在发生排斥反应的同种异体移植肿瘤（3-甲基胆蒽诱导的腹水型肿瘤细胞）细胞中，IDO被显著（约50倍）诱导，并且该酶是由同种异体移植肿瘤细胞与浸润白细胞相互作用释放的因子所诱导。在肿瘤移植后第7天收获的浸润白细胞的培养上清液，在肿瘤细胞中诱导出最高的IDO活性。通过添加抗IFN-γ抗体可完全中和诱导活性，但抗IFN-α/β抗体则不能。用ELISA法在含有2×10⁶个白细胞/ml的12小时培养上清液中检测到约6 U/ml的IFN-γ，6 U/ml的重组IFN-γ在3-甲基胆蒽诱导的腹水型肿瘤细胞中诱导IDO的程度与培养上清液中的IFN-γ相同。此外，腹腔注射抗IFN-γ抗体几乎完全抑制了同种异体移植肿瘤细胞中IDO的诱导。这些观察结果表明，同种异体移植肿瘤细胞中负责诱导IDO的因子是IFN-γ。
