Nocella Cristina, D'Amico Alessandra, Cammisotto Vittoria, Bartimoccia Simona, Castellani Valentina, Loffredo Lorenzo, Marini Leonardo, Ferrara Giulia, Testa Matteo, Motta Giulio, Benazzi Beatrice, Zara Fabio, Frati Giacomo, Sciarretta Sebastiano, Pignatelli Pasquale, Violi Francesco, Carnevale Roberto, Group Smile
Department of Clinical Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy.
Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", 00135 Rome, Italy.
Antioxidants (Basel). 2023 Feb 9;12(2):429. doi: 10.3390/antiox12020429.
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is a multisubunit enzyme complex that participates in the generation of superoxide or hydrogen peroxide (HO) and plays a key role in several biological functions. Among seven known NOX isoforms, NOX2 was the first identified in phagocytes but is also expressed in several other cell types including endothelial cells, platelets, microglia, neurons, and muscle cells. NOX2 has been assigned multiple roles in regulating many aspects of innate and adaptive immunity, and human and mouse models of NOX2 genetic deletion highlighted this key role. On the other side, NOX2 hyperactivation is involved in the pathogenesis of several diseases with different etiologies but all are characterized by an increase in oxidative stress and inflammatory process. From this point of view, the modulation of NOX2 represents an important therapeutic strategy aimed at reducing the damage associated with its hyperactivation. Although pharmacological strategies to selectively modulate NOX2 are implemented thanks to new biotechnologies, this field of research remains to be explored. Therefore, in this review, we analyzed the role of NOX2 at the crossroads between immunity and pathologies mediated by its hyperactivation. We described (1) the mechanisms of activation and regulation, (2) human, mouse, and cellular models studied to understand the role of NOX2 as an enzyme of innate immunity, (3) some of the pathologies associated with its hyperactivation, and (4) the inhibitory strategies, with reference to the most recent discoveries.
烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOX）是一种多亚基酶复合物，参与超氧化物或过氧化氢（H₂O₂）的生成，并在多种生物学功能中起关键作用。在已知的七种NOX亚型中，NOX2是最早在吞噬细胞中发现的，但也在包括内皮细胞、血小板、小胶质细胞、神经元和肌肉细胞在内的其他几种细胞类型中表达。NOX2在调节先天免疫和适应性免疫的许多方面发挥了多种作用，NOX2基因缺失的人类和小鼠模型突出了这一关键作用。另一方面，NOX2的过度激活参与了多种病因不同的疾病的发病机制，但所有这些疾病的特征都是氧化应激和炎症过程增加。从这个角度来看，调节NOX2代表了一种重要的治疗策略，旨在减少与其过度激活相关的损伤。尽管借助新生物技术实施了选择性调节NOX2的药理学策略，但这一研究领域仍有待探索。因此，在本综述中，我们分析了NOX2在免疫与由其过度激活介导的病理之间的交叉点上的作用。我们描述了（1）激活和调节机制，（2）为了解NOX2作为先天免疫酶的作用而研究的人类、小鼠和细胞模型，（3）与其过度激活相关的一些病理，以及（4）参考最新发现的抑制策略。
