PDF(Pubmed)
Abstract：
Pyroptosis represents a type of cell death mechanism notable for its cell membrane disruption and the subsequent release of proinflammatory cytokines. The Nod-like receptor family pyrin domain containing inflammasome 3 (NLRP3) plays a critical role in the pyroptosis mechanism associated with various diseases resulting from particulate matter (PM) exposure. Tert-butylhydroquinone (tBHQ) is a synthetic antioxidant commonly used in a variety of foods and products. The aim of this study is to examine the potential of tBHQ as a therapeutic agent for managing sinonasal diseases induced by PM exposure. The occurrence of NLRP3 inflammasome-dependent pyroptosis in RPMI 2650 cells treated with PM < 4 µm in size was confirmed using Western blot analysis and enzyme-linked immunosorbent assay results for the pyroptosis metabolites IL-1β and IL-18. In addition, the inhibitory effect of tBHQ on PM-induced pyroptosis was confirmed using Western blot and immunofluorescence techniques. The inhibition of tBHQ-mediated pyroptosis was abolished upon nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown, indicating its involvement in the antioxidant mechanism. tBHQ showed potential as a therapeutic agent for sinonasal diseases induced by PM because NLRP3 inflammasome activation was effectively suppressed via the Nrf2 pathway.
摘要：
细胞凋亡代表一种细胞死亡机制，其细胞膜破坏和随后释放促炎细胞因子。含有炎性体3（NLRP3）的Nod样受体家族pyrin结构域在与颗粒物（PM）暴露引起的各种疾病相关的焦亡机制中起关键作用。叔丁基对苯二酚（tBHQ）是一种合成抗氧化剂，通常用于各种食品和产品中。这项研究的目的是研究tBHQ作为治疗由PM暴露引起的鼻窦疾病的治疗剂的潜力。使用Westernblot分析和酶联免疫吸附测定结果证实了用PM<4µm大小处理的RPMI2650细胞中NLRP3炎性体依赖性焦亡的发生。此外,使用Westernblot和免疫荧光技术证实了tBHQ对PM诱导的焦亡的抑制作用。在核因子红系2相关因子2（Nrf2）敲低后，tBHQ介导的焦亡的抑制被废除，表明它参与了抗氧化机制。由于通过Nrf2途径有效抑制了NLRP3炎性体的激活，因此tBHQ显示出作为PM诱导的鼻窦疾病的治疗剂的潜力。
