Reversal of an interferon-gamma-resistant phenotype by poly(I:C): possible role of double-stranded RNA-activated kinase in interferon-gamma signaling.
Reversal of an interferon-gamma-resistant phenotype by poly(I:C): possible role of double-stranded RNA-activated kinase in interferon-gamma signaling.
复制标题
Poly(I:C) 逆转干扰素-γ 抗性表型：双链 RNA 激活激酶在干扰素-γ 信号传导中的可能作用。
DOI：
10.1089/jir.1993.13.283
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Taylor,MW
中科院分区：
文献类型：
--
作者：
Ozes,ON;Taylor,MW
吲哚胺2，3-双加氧酶（IDO）在肿瘤细胞系中由干扰素-γ（IFN-γ）处理诱导。在ME 180宫颈癌细胞中，在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。ME 180的IFN-γ抗性突变体IR 3B 6 B在IFN-γ处理后表达非常低水平的IDO信息。然而，用poly（I：C）预处理该突变体恢复了IDO mRNA和IDO酶活性的正常水平。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的诱导，用IFN-γ处理的ME 180和IR 3B 6 B细胞制备的免疫沉淀p68激酶体外磷酸化小牛胸腺组蛋白，发现IFN-γ处理后IR 3B 6 B细胞中该激酶的活化缺陷，而Poly（I：C）处理该突变细胞可恢复p68激酶活性。从这些结果，我们得出结论，双链RNA依赖性激酶被IFN-γ处理激活，并且其激活与IFN-γ介导的IDO基因诱导相关。
Indoleamine 2,3-dioxygenase (IDO) is induced in neoplastic cell lines by interferon-γ (IFN-γ) treatment. In ME180 cervical carcinoma cells, there is a rapid increase in IDO mRNA accumulation beginning at 4 h after IFN-γ treatment and continuing for at least 24 h. The IFN-γ-resistant mutant of ME180, IR3B6B, expresses very low levels of IDO message after IFN-γ 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-γresistant phenotype and induction of IDO mRNA are inhibited by 2-aminopurine.In vitrophosphorylation of calf thymus histone using the immunoprecipitated p68 kinase prepared from IFN-γ-treated ME180 and IR3B6B cells revealed the deficiency of activation of this kinase in IR3B6B cells after IFN-γ 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-γ treatment and its activation correlates with IFN-γ-mediated induction of the IDO gene.