Li Cantao, Wu Chenxi, Li Fenfen, Xu Wenjing, Zhang Xiaoxi, Huang Yan, Xia Daozong
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People's Republic of China.
J Inflamm Res. 2024 Mar 19;17:1735-1763. doi: 10.2147/JIR.S460333. eCollection 2024.
Gouty arthritis (GA) is an immune-mediated disorder characterized by severe inflammation due to the deposition of monosodium urate (MSU) crystals in the joints. The pathophysiological mechanisms of GA are not yet fully understood, and therefore, the identification of effective therapeutic targets is of paramount importance. Neutrophil extracellular traps (NETs), an intricate structure of DNA scaffold, encompassing myeloperoxidase, histones, and elastases - have gained significant attention as a prospective therapeutic target for gouty arthritis, due to their innate antimicrobial and immunomodulatory properties. Hence, exploring the therapeutic potential of NETs in gouty arthritis remains an enticing avenue for further investigation. During the process of gouty arthritis, the formation of NETs triggers the release of inflammatory cytokines, thereby contributing to the inflammatory response, while MSU crystals and cytokines are sequestered and degraded by the aggregation of NETs. Here, we provide a concise summary of the inflammatory processes underlying the initiation and resolution of gouty arthritis mediated by NETs. Furthermore, this review presents an overview of the current pharmacological approaches for treating gouty arthritis and summarizes the potential of natural and synthetic product-based inhibitors that target NET formation as novel therapeutic options, alongside elucidating the intrinsic challenges of these inhibitors in NETs research. Lastly, the limitations of HL-60 cell as a suitable substitute of neutrophils in NETs research are summarized and discussed. Series of recommendations are provided, strategically oriented towards guiding future investigations to effectively address these concerns. These findings will contribute to an enhanced comprehension of the interplay between NETs and GA, facilitating the proposition of innovative therapeutic strategies and novel approaches for the management of GA.
痛风性关节炎（GA）是一种免疫介导的疾病，其特征是由于单钠尿酸盐（MSU）晶体在关节中沉积而导致严重炎症。GA的病理生理机制尚未完全阐明，因此，确定有效的治疗靶点至关重要。中性粒细胞胞外陷阱（NETs）是一种由DNA支架构成的复杂结构，包含髓过氧化物酶、组蛋白和弹性蛋白酶，由于其固有的抗菌和免疫调节特性，作为痛风性关节炎的潜在治疗靶点受到了广泛关注。因此，探索NETs在痛风性关节炎中的治疗潜力仍然是一个诱人的进一步研究途径。在痛风性关节炎过程中，NETs的形成触发炎症细胞因子的释放，从而促进炎症反应，而MSU晶体和细胞因子则被NETs的聚集所隔离和降解。在此，我们简要总结了NETs介导的痛风性关节炎起始和消退的炎症过程。此外，本综述概述了目前治疗痛风性关节炎的药理学方法，总结了以天然和合成产物为基础的靶向NET形成的抑制剂作为新型治疗选择的潜力，同时阐明了这些抑制剂在NETs研究中的内在挑战。最后，总结并讨论了HL-60细胞作为NETs研究中中性粒细胞合适替代物的局限性。提供了一系列建议，旨在指导未来的研究以有效解决这些问题。这些发现将有助于增强对NETs与GA之间相互作用的理解，促进提出创新的治疗策略和管理GA的新方法。
