Marked increases in hippocampal neuron indoleamine 2, 3-dioxygenase via IFN-γ-independent pathway following transient global ischemia in mouse
Marked increases in hippocampal neuron indoleamine 2, 3-dioxygenase via IFN-γ-independent pathway following transient global ischemia in mouse
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DOI：
10.1016/j.neures.2008.12.003
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发表时间：
2009-03-01
影响因子：
2.9
通讯作者：
Seishima, Mitsuru
中科院分区：
文献类型：
--
作者：
Hoshi, Masato;Saito, Kuniaki;Seishima, Mitsuru
吲哚胺2，3-双加氧酶（IDO），其将L-色氨酸（L-TRP）分解代谢为L-犬尿氨酸（L-KYN），是通过干扰素-γ（IFN-γ）依赖性和/或非依赖性机制上调的免疫调节因子。在这项研究中，我们研究了IDO的定位和诱导IDO的表达是否是一个IFN-γ依赖性和/或非依赖性的机制，在中枢神经系统脑缺血后。采用免疫组织化学、免疫荧光和RT-PCR方法检测缺血后不同时间点IDO蛋白和mRNA的表达。短暂性全脑缺血72 h后，海马神经元IDO mRNA和免疫组化染色均显著上调。虽然IFN-γ是IDO的主要诱导物，但海马神经元IDO在IFN-γ KO小鼠中明显上调。总之，这是第一个发现，在短暂性全脑缺血后，海马神经元中IDO的上调通过INF-γ非依赖性机制发生。(C)2009年由Elsevier爱尔兰有限公司和日本神经科学学会出版。
Indoleamine 2,3-dioxygenase (IDO), which catabolizes L-tryptophan (L-TRP) to L-kynurenine (L-KYN), is an immunoregulatory factor that is up-regulated via an interferon-gamma (IFN-gamma)-dependent and/or independent mechanism. In this study, we investigated the localization of IDO and whether induction of IDO expression is an IFN-gamma-dependent and/or -independent mechanism in the CNS after cerebral ischemia. The expressions of IDO protein and mRNA were investigated at different time points following cerebral ischemia using immunohistochemistry, immunofluorescence and RT-PCR. Hippocampal neuron IDO mRNA and immunohistochemical staining were significantly up-regulated 72 h after transient global ischemia. Although IFN-gamma is a dominant inducer of IDO, hippocampal neuron IDO was clearly up-regulated in IFN-gamma KO mice. In summary, this is the first finding that up-regulation of IDO in hippocampal neurons after transient global ischemia occurs via INF-gamma-independent mechanisms. (C) 2009 Published by Elsevier Ireland Ltd and the Japan Neuroscience Society.