Indoleamine 2,3 dioxygenase in intestinal disease.
Indoleamine 2,3 dioxygenase in intestinal disease.
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DOI：
10.1097/mog.0b013e32835c9cb3
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发表时间：
2013-03
影响因子：
2.5
通讯作者：
Ciorba MA
中科院分区：
文献类型：
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作者：
Ciorba MA
包括炎症性肠病（IBD）和恶性肿瘤在内的几种胃肠道疾病与吲哚胺2，3双加氧酶-1（IDO 1）的表达升高相关。IDO 1启动色氨酸催化沿着产生几种生物活性的基于犬尿氨酸的代谢物的途径。促进T细胞介导的耐受性和抗微生物作用是归因于IDO 1活性的多种功能之一。本文综述了肠道相关IDO 1表达的各种影响的最新进展。在活动性IBD中，IDO 1在固有层和上皮细胞中高度表达。实验模型表明，IDO 1通过限制炎症反应和保护上皮细胞来促进肠道免疫稳态。在人结肠癌中，肿瘤上皮细胞IDO 1的高表达与不良预后相关。血清犬尿氨酸：色氨酸比率在活动性克罗恩病和结肠癌中均升高，表明该测量可证明可用作疾病生物标志物。IDO 1抑制剂已进入临床试验，为晚期恶性肿瘤的免疫治疗提供了新的希望。IDO 1活性显著影响胃肠道疾病的病理生理学和严重程度。IDO 1活性的测量可能用作疾病生物标志物。IDO 1活性的调控具有治疗炎症和恶性肿瘤相关胃肠道疾病的巨大潜力。
Several gastrointestinal diseases including the inflammatory bowel diseases (IBD) and malignancy are associated with elevated expression of indoleamine 2,3 dioxygenase-1 (IDO1). IDO1 initiates tryptophan catabolism along a pathway that generates several bioactive kynurenine-based metabolites. Promotion of T-cell mediated tolerance and antimicrobial effects are among the variety of functions attributed to IDO1 activity. Recent advances addressing the diverse implications of gut associated IDO1 expression are herein reviewed. In active IBD IDO1 is highly expressed both in cells of the lamina propria and epithelium. Experimental models demonstrate that IDO1 promotes gut immune homeostasis by limiting inflammatory responses and protecting the epithelium. In human colon cancer, high expression of IDO1 by the neoplastic epithelium correlates with poor prognosis. The serum kynurenine:tryptophan ratio is elevated in both active Crohn’s disease and in colon cancer suggesting this measurement may prove useful as a disease biomarker. IDO1 inhibitors have moved to clinical trials providing new hope as immunotherapy for advanced malignancy. IDO1 activity significantly shapes gastrointestinal disease pathophysiology and severity. Measures of IDO1 activity may be useful as a disease biomarker. Manipulation of IDO1 activity has great potential as treatment for both inflammatory and malignancy associated gastrointestinal disease.