Indoleamine 2,3-dioxygenase is highly expressed in human adult T-cell leukemia/lymphoma and chemotherapy changes tryptophan catabolism in serum and reduced activity
Indoleamine 2,3-dioxygenase is highly expressed in human adult T-cell leukemia/lymphoma and chemotherapy changes tryptophan catabolism in serum and reduced activity
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DOI：
10.1016/j.leukres.2008.05.023
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发表时间：
2009-01-01
影响因子：
2.7
通讯作者：
Seishima, Mitsuru
中科院分区：
文献类型：
--
作者：
Hoshi, Masato;Ito, Hiroyasu;Seishima, Mitsuru
成人t细胞白血病/淋巴瘤（ATLL）是由人类t细胞嗜淋巴病毒I型（HTLV-1）引起的。吲哚胺2,3-双加氧酶（IDO）是l -色氨酸（L-TRP）降解酶，在几种不同类型的免疫细胞的强大免疫调节作用中起关键作用。在本研究中，我们研究了IDO在ATLL细胞中的表达以及化疗对ATLL患者IDO启动L-TRP分解代谢的影响。ATLL患者血清l -犬尿氨酸（L-KYN）浓度、L-KYN/L-TRP比值以及ATLL细胞IDO mRNA表达水平均显著高于健康人和htlv阳性携带者。另一方面，与健康受试者相比，ATLL患者的L-TRP水平显著降低。免疫组化染色显示，IDO在ATLL细胞细胞质中表达强烈。有趣的是，化疗后血清L-KYN和可溶性IL-2受体浓度显著降低，L-TRP浓度显著升高。这些数据提供了IDO在ATLL细胞中高表达的证据，并且IDO启动的L-TRP分解代谢随化疗而改变。(C) 2008 Elsevier Ltd版权所有。
Adult T-cell leukemia/lymphoma (ATLL) is caused by human T-cell lymphotropic virus type I (HTLV-1). Indoleamine 2,3-dioxygenase (IDO), the L-tryptophan (L-TRP)-degrading enzyme, plays a key role in the powerful immunomodulatory effects of several different types of immune cells. In this study, we investigated the IDO expression in ATLL cells and the effect of chemotherapy on IDO-initiating L-TRP catabolism in patients with ATLL. Serum L-kynurenine (L-KYN) concentrations, L-KYN/L-TRP ratio, and the level of IDO mRNA expression in ATLL cells were significantly increased in ATLL patients compared to those in healthy and HTLV-positive carrier subjects. On the other hand, L-TRP level was significantly decreased in ATLL patients compared to that in healthy subjects. In the immunohistochemical staining, IDO was strongly expressed in cytoplasm of ATLL cells. Interestingly, serum L-KYN as well as soluble IL-2 receptor concentrations was significantly reduced, and L-TRP concentrations were significantly increased after chemotherapy. These data provide evidence that IDO is highly expressed in ATLL cells, and that IDO-initiating L-TRP catabolism changes with chemotherapy. (C) 2008 Elsevier Ltd. All rights reserved.