嘌呤能系统作为治疗免疫介导的炎症性疾病的药理学靶点。
The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inflammatory Diseases.
机构信息
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.A., C.B.); Laboratory of Cardiovascular Physiology and Tissue Injury, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (P.P.); and Department of Anesthesiology, Columbia University, New York, New York (G.H.).
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.A., C.B.); Laboratory of Cardiovascular Physiology and Tissue Injury, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (P.P.); and Department of Anesthesiology, Columbia University, New York, New York (G.H.)
出版信息
Pharmacol Rev. 2019 Jul;71(3):345-382. doi: 10.1124/pr.117.014878.
Immune-mediated inflammatory diseases (IMIDs) encompass a wide range of seemingly unrelated conditions, such as multiple sclerosis, rheumatoid arthritis, psoriasis, inflammatory bowel diseases, asthma, chronic obstructive pulmonary disease, and systemic lupus erythematosus. Despite differing etiologies, these diseases share common inflammatory pathways, which lead to damage in primary target organs and frequently to a plethora of systemic effects as well. The purinergic signaling complex comprising extracellular nucleotides and nucleosides and their receptors, the P2 and P1 purinergic receptors, respectively, as well as catabolic enzymes and nucleoside transporters is a major regulatory system in the body. The purinergic signaling complex can regulate the development and course of IMIDs. Here we provide a comprehensive review on the role of purinergic signaling in controlling immunity, inflammation, and organ function in IMIDs. In addition, we discuss the possible therapeutic applications of drugs acting on purinergic pathways, which have been entering clinical development, to manage patients suffering from IMIDs.
免疫介导的炎症性疾病（IMIDs）涵盖了广泛的看似无关的疾病，如多发性硬化症、类风湿性关节炎、银屑病、炎症性肠病、哮喘、慢性阻塞性肺疾病和系统性红斑狼疮。尽管这些疾病的病因不同，但它们都具有共同的炎症途径，这些途径导致主要靶器官的损伤，并经常导致大量的全身影响。由细胞外核苷酸和核苷及其受体（分别为 P2 和 P1 嘌呤能受体）以及代谢酶和核苷转运体组成的嘌呤能信号复合物是体内的主要调节系统。嘌呤能信号复合物可以调节 IMIDs 的发展和病程。在这里，我们全面回顾了嘌呤能信号在控制 IMIDs 中的免疫、炎症和器官功能中的作用。此外，我们还讨论了作用于嘌呤能途径的药物的可能治疗应用，这些药物已进入临床开发阶段，以治疗患有 IMIDs 的患者。
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