IDO1和IDO2表达在人类肿瘤:左旋的——但不是dextro-1-methyl色氨酸抑制色氨酸分解代谢。
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Lob年代,Konigsrainer, Zieker D,布鲁赫提单,Rammensee HG, Opelz G, Terness P
IDO1和IDO2表达在人类肿瘤:左旋的——但不是dextro-1-methyl色氨酸抑制色氨酸分解代谢。
癌症Immunol Immunother。2009年1月,58 (1):153 - 7。doi: 10.1007 / s00262 - 008 - 0513 - 6。Epub 2008年4月17日。
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18418598 (在PubMed]
- 文摘
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目标:Indoleamine-2 3-Dioxygenase (IDO)是一种免疫抑制分子诱导在各种细胞。除了经典的被罩(IDO1),一个新的变种,IDO2,最近被描述。当表达的树突状细胞(dc)或癌细胞,被罩被认为抑制肿瘤的免疫反应。小说在癌症治疗方法设想抑制被罩1-methyl-tryptophan(1吨)。IDO1 levo-isoform (L-1MT)块,而dextro-1MT (D-1MT),用于临床试验,抑制IDO2。这里我们分析IDO2表达在人类癌症细胞和的影响都1-MT亚型在语言活动。方法:手术报告证实人类原发性肿瘤以及人类癌症细胞系被rt - pcr检测IDO1和IDO2表达。IDO1活动的海拉细胞被转染IDO1-specific siRNA和分析色氨酸,rp -退化。D-1MT的影响和L-1MT被罩活动人类结肠癌的海拉细胞和蛋白质的分离进行了研究。结果:人类原发性胃,结肠和肾细胞癌持续表达,IDO1和IDO2信使rna,而癌细胞线必须诱导移行细胞(IFN-gamma)。 Treatment of Hela cells with IDO1-specific siRNA resulted in complete abrogation of tryptophan degradation. Only L-1MT, and not D-1MT, was able to block IDO activity in IFN-gamma-treated Hela cells as well as in protein isolates of primary human colon cancer. CONCLUSIONS: Although IDO2 is expressed in human tumors, tryptophan degradation is entirely provided by IDO1. Importantly, D-1MT does not inhibit the IDO activity of malignant cells. If ongoing clinical studies show a therapeutic effect of D-1MT, this cannot be attributed to inhibition of IDO in tumor cells.