Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Departments of Pediatrics, The Pennsylvania State University, College of Medicine, Hershey, PA, USA.
The Feinstein Institute for Medical Research, Center for Autoimmune and Musculoskeletal Diseases, Manhasset, NY, USA.
Pharmacol Ther. 2018 Jan;181:169-182. doi: 10.1016/j.pharmthera.2017.08.011. Epub 2017 Aug 23.
Asthma is a complex inflammatory disease characterized by airway inflammation and hyperresponsiveness. The mechanisms associated with the development and progression of asthma have been widely studied in multiple populations and animal models, and these have revealed involvement of various cell types and activation of intracellular signaling pathways that result in activation of inflammatory genes. Significant contributions of Toll-like-receptors (TLRs) and transcription factors such as NF-кB, have been reported as major contributors to inflammatory pathways. These have also recently been associated with mechanisms of oxidative biology. This is of important clinical significance as the observed inefficacy of current available treatments for severe asthma is widely attributed to oxidative stress. Therefore, targeting oxidizing molecules in conjunction with inflammatory mediators and transcription factors may present a novel therapeutic strategy for asthma. In this review, we summarize TLRs and NF-кB pathways in the context of exacerbation of asthma pathogenesis and oxidative biology, and we discuss the potential use of polyphenolic flavonoid compounds, known to target these pathways and possess antioxidant activity, as potential therapeutic agents for asthma.
哮喘是一种复杂的炎症性疾病，其特征为气道炎症和高反应性。在多个人群和动物模型中广泛研究了与哮喘发生和发展相关的机制，这些研究揭示了各种细胞类型的参与和细胞内信号通路的激活，从而导致炎症基因的激活。Toll 样受体 (TLRs) 和转录因子（如 NF-кB）的重要贡献被报道为炎症途径的主要贡献者。这些最近也与氧化生物学的机制有关。这在临床上具有重要意义，因为目前用于严重哮喘的治疗方法的观察到的无效性被广泛归因于氧化应激。因此，针对氧化分子以及炎症介质和转录因子可能为哮喘提供一种新的治疗策略。在这篇综述中，我们总结了 TLRs 和 NF-кB 途径在哮喘发病机制和氧化生物学中的作用，并讨论了已知针对这些途径并具有抗氧化活性的多酚类黄酮化合物作为哮喘潜在治疗药物的潜在用途。
