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吲哚胺 2,3-双加氧酶/犬尿氨酸; 治疗炎症性疾病的新见解。

IDO/Kynurenine; novel insight for treatment of inflammatory diseases.

机构信息

Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Cytokine. 2023 Jun;166:156206. doi: 10.1016/j.cyto.2023.156206. Epub 2023 Apr 28.

Abstract

Inflammation and oxidative stress play pivotal roles in pathogenesis of many diseases including cancer, type 2 diabetes, cardiovascular disease, atherosclerosis, neurological diseases, and inflammatory diseases such as inflammatory bowel disease (IBD). Inflammatory mediators such as interleukins (ILs), interferons (INF-s), and tumor necrosis factor (TNF)-α are related to an extended chance of inflammatory diseases initiation or progression due to the over expression of the nuclear factor Kappa B (NF-κB), signal transducer of activators of transcription (STAT), nod-like receptor family protein 3 (NLRP), toll-like receptors (TLR), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways. These pathways are completely interconnected. Theindoleamine 2,3 dioxygenase (IDO) subset of the kynurenine (KYN) (IDO/KYN), is a metabolic inflammatory pathway involved in production of nicotinamide adenine dinucleotide (NAD + ). It has been shown that IDO/KYN actively participates in inflammatory processes and can increase the secretion of cytokines that provoke inflammatory diseases. Data were extracted from clinical and animal studies published in English between 1990-April 2022, which were collected from PubMed, Google Scholar, Scopus, and Cochrane library. IDO/KYN is completely associated with inflammatory-related pathways, thus leading to the production of cytokines such as TNF-α, IL-1β, and IL-6, and ultimately development and progression of various inflammatory disorders. Inhibition of the IDO/KYN pathway might be a novel therapeutic option for inflammatory diseases. Herein, we gathered data on probable interactions of the IDO/KYN pathway with induction of some inflammatory diseases.

摘要

炎症和氧化应激在许多疾病的发病机制中起着关键作用,包括癌症、2 型糖尿病、心血管疾病、动脉粥样硬化、神经退行性疾病和炎症性疾病,如炎症性肠病 (IBD)。白细胞介素 (ILs)、干扰素 (INF-s) 和肿瘤坏死因子 (TNF)-α 等炎症介质与核因子 Kappa B (NF-κB)、转录激活物的信号转导子 (STAT)、核苷酸结合寡聚化结构域样受体家族蛋白 3 (NLRP)、Toll 样受体 (TLR)、丝裂原激活的蛋白激酶 (MAPK) 和哺乳动物雷帕霉素靶蛋白 (mTOR) 途径的过度表达有关,这些途径与炎症性疾病的发生或进展有关。这些途径是完全相互关联的。色氨酸 2,3 双加氧酶 (IDO) 分支的犬尿氨酸 (KYN) (IDO/KYN) 是一种代谢性炎症途径,参与烟酰胺腺嘌呤二核苷酸 (NAD+) 的产生。已经表明,IDO/KYN 积极参与炎症过程,并能增加引发炎症性疾病的细胞因子的分泌。数据从 1990 年至 2022 年 4 月发表的英语临床和动物研究中提取,这些研究来自 PubMed、Google Scholar、Scopus 和 Cochrane 图书馆。IDO/KYN 与炎症相关途径完全相关,从而导致 TNF-α、IL-1β 和 IL-6 等细胞因子的产生,并最终导致各种炎症性疾病的发生和发展。抑制 IDO/KYN 途径可能是治疗炎症性疾病的一种新的治疗选择。在此,我们收集了关于 IDO/KYN 途径与一些炎症性疾病发生的可能相互作用的数据。

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