Department of Pathology and Laboratory Medicine, The Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, VT, USA.
Vermont Lung Center, University of Vermont, Burlington, VT, USA.
Br J Pharmacol. 2018 May;175(9):1401-1418. doi: 10.1111/bph.14158. Epub 2018 Mar 15.
NADPH oxidases (NOXs) represent a family of enzymes that mediate regulated cellular production of reactive oxygen species (ROS) and play various functional roles in physiology. Among the NOX family, the dual oxidases DUOX1 and DUOX2 are prominently expressed in epithelial cell types at mucosal surfaces and have therefore been considered to have important roles in innate host defence pathways. Recent studies have revealed important insights into the host defence mechanisms of DUOX enzymes, which control innate immune response pathways in response to either microbial or allergic triggers. In this review, we discuss the current level of understanding with respect to the biological role(s) of DUOX enzymes and the unique role of DUOX1 in mediating innate immune responses to epithelial injury and allergens and in the development of allergic disease. These novel findings highlight DUOX1 as an attractive therapeutic target, and opportunities for the development of selective inhibitor strategies will be discussed.
烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NOXs)家族是一类能够调节细胞内活性氧(ROS)产生的酶,在生理学中具有多种功能作用。在 NOX 家族中,双氧化酶 DUOX1 和 DUOX2 在黏膜表面的上皮细胞类型中大量表达,因此被认为在先天宿主防御途径中具有重要作用。最近的研究揭示了 DUOX 酶的宿主防御机制的重要见解,这些机制控制着对微生物或过敏原的先天免疫反应途径。在这篇综述中,我们讨论了目前对 DUOX 酶的生物学作用及其在介导上皮损伤和过敏原引起的先天免疫反应以及过敏疾病发展中的独特作用的理解水平。这些新发现强调了 DUOX1 作为一个有吸引力的治疗靶点,同时也讨论了开发选择性抑制剂策略的机会。