Ozes O N, Taylor M W
Department of Biology, Indiana University, Bloomington 47405.
J Interferon Res. 1993 Aug;13(4):283-8. doi: 10.1089/jir.1993.13.283.
Indoleamine 2,3-dioxygenase (IDO) is induced in neoplastic cell lines by interferon-gamma (IFN-gamma) treatment. In ME180 cervical carcinoma cells, there is a rapid increase in IDO mRNA accumulation beginning at 4 h after IFN-gamma treatment and continuing for at least 24 h. The IFN-gamma-resistant mutant of ME180, IR3B6B, expresses very low levels of IDO message after IFN-gamma treatment. However, pretreatment of this mutant with poly(I:C) restores normal levels of IDO mRNAs and IDO enzyme activity. Poly(I:C) mediated reversal of the IFN-gamma-resistant phenotype and induction of IDO mRNA are inhibited by 2-aminopurine. In vitro phosphorylation of calf thymus histone using the immunoprecipitated p68 kinase prepared from IFN-gamma-treated ME180 and IR3B6B cells revealed the deficiency of activation of this kinase in IR3B6B cells after IFN-gamma treatment, and treatment of this mutant cells with poly(I:C) restores p68 kinase activity. From these results, we conclude that a double-stranded RNA-dependent kinase is activated by IFN-gamma treatment and its activation correlates with IFN-gamma-mediated induction of the IDO gene.
吲哚胺2,3-双加氧酶（IDO）在肿瘤细胞系中经γ干扰素（IFN-γ）处理后被诱导。在ME180宫颈癌细胞中，IFN-γ处理后4小时开始，IDO mRNA积累迅速增加，并持续至少24小时。ME180的IFN-γ抗性突变体IR3B6B在IFN-γ处理后表达极低水平的IDO信息。然而，用聚肌胞苷酸（poly(I:C)）预处理该突变体可恢复IDO mRNA的正常水平和IDO酶活性。2-氨基嘌呤可抑制poly(I:C)介导的IFN-γ抗性表型逆转和IDO mRNA诱导。使用从IFN-γ处理的ME180和IR3B6B细胞制备的免疫沉淀p68激酶对小牛胸腺组蛋白进行体外磷酸化，结果显示IFN-γ处理后IR3B6B细胞中该激酶的激活存在缺陷，用poly(I:C)处理该突变体细胞可恢复p68激酶活性。从这些结果中，我们得出结论，双链RNA依赖性激酶经IFN-γ处理后被激活，其激活与IFN-γ介导的IDO基因诱导相关。
