Zhou Yunxin, Zhang Fan, Ding Junying
Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing Institute of Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China.
Immune Netw. 2022 Jun 20;22(3):e21. doi: 10.4110/in.2022.22.e21. eCollection 2022 Jun.
As far the current severe coronavirus disease 2019 (COVID-19), respiratory disease is still the biggest threat to human health. In addition, infectious respiratory diseases are particularly prominent. In addition to killing and clearing the infection pathogen directly, regulating the immune responses against the pathogens is also an important therapeutic modality. Sirtuins belong to NAD+-dependent class III histone deacetylases. Among 7 types of sirtuins, silent information regulator type-1 (SIRT1) played a multitasking role in modulating a wide range of physiological processes, including oxidative stress, inflammation, cell apoptosis, autophagy, antibacterial and antiviral functions. It showed a critical effect in regulating immune responses by deacetylation modification, especially through high-mobility group box 1 (HMGB1), a core molecule regulating the immune system. SIRT1 was associated with many respiratory diseases, including COVID-19 infection, bacterial pneumonia, tuberculosis, and so on. Here, we reviewed the latest research progress regarding the effects of SIRT1 on immune system in respiratory diseases. First, the structure and catalytic characteristics of SIRT1 were introduced. Next, the roles of SIRT1, and the mechanisms underlying the immune regulatory effect through HMGB1, as well as the specific activators/inhibitors of SIRT1, were elaborated. Finally, the multitasking roles of SIRT1 in several respiratory diseases were discussed separately. Taken together, this review implied that SIRT1 could serve as a promising specific therapeutic target for the treatment of respiratory diseases.
就目前的重症冠状病毒病2019（COVID-19）而言，呼吸系统疾病仍然是对人类健康的最大威胁。此外，传染性呼吸系统疾病尤为突出。除了直接杀死和清除感染病原体外，调节针对病原体的免疫反应也是一种重要的治疗方式。沉默调节蛋白属于依赖烟酰胺腺嘌呤二核苷酸（NAD+）的Ⅲ类组蛋白脱乙酰酶。在7种沉默调节蛋白类型中，沉默信息调节因子1（SIRT1）在调节广泛的生理过程中发挥着多方面作用，包括氧化应激、炎症、细胞凋亡、自噬、抗菌和抗病毒功能。它通过去乙酰化修饰在调节免疫反应中显示出关键作用，特别是通过高迁移率族蛋白B1（HMGB1），这是一种调节免疫系统的核心分子。SIRT1与许多呼吸系统疾病相关，包括COVID-19感染、细菌性肺炎、肺结核等。在此，我们综述了关于SIRT1对呼吸系统疾病免疫系统影响的最新研究进展。首先，介绍了SIRT1的结构和催化特性。接下来，阐述了SIRT1的作用、通过HMGB1产生免疫调节作用的机制以及SIRT1的特异性激活剂/抑制剂。最后，分别讨论了SIRT1在几种呼吸系统疾病中的多方面作用。综上所述，本综述表明SIRT1有望成为治疗呼吸系统疾病的特异性治疗靶点。
