College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, Gwangju, 61186, Republic of Korea; College of Veterinary Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.
College of Veterinary Medicine (BK21 Plus Project Team), Chonnam National University, Gwangju, 61186, Republic of Korea.
Regul Toxicol Pharmacol. 2020 Apr;112:104618. doi: 10.1016/j.yrtph.2020.104618. Epub 2020 Feb 19.
Silica dioxide nanoparticles (SiONPs) are mainly used in the rubber industry; however, they are a major air pollutant in Asia. Thus, extensive research on this issue is required. In this study, we investigated the effects of SiONPs on asthma aggravation and elucidated the underlying mechanism using ovalbumin (OVA)-induced asthmatic mice model and in NCI-H292 cells. Mice exposed to SiONPs showed markedly increased Penh values, inflammatory cell counts, and inflammatory cytokine levels compared to OVA-induced asthmatic mice. Exposure to SiONPs also induced additional airway inflammation and mucus secretion with increases in protein expression levels of thioredoxin-interacting protein (TXNIP), NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, and interleukin (IL)-1β compared to those in OVA-induced asthmatic mice. Treatment of SiONPs in NCI-H292 cells also significantly increased mRNA expression levels of inflammatory cytokines accompanied with elevation in the levels of TXNIP, NLRP3 inflammasome, and IL-1β proteins in a concentration-dependent manner. Taken together, exposure to SiONPs aggravated asthma development, which is closely related to inflammasome activation. Our results provide useful information about the toxicological effects of SiONPs on asthma exacerbation and suggest the need to avoid SiONP exposure especially in individuals with respiratory diseases.
二氧化硅纳米粒子(SiONPs)主要用于橡胶工业;然而,它们也是亚洲地区的主要空气污染物。因此,需要对此问题进行广泛研究。在本研究中,我们使用卵清蛋白(OVA)诱导的哮喘小鼠模型和 NCI-H292 细胞研究了 SiONPs 对哮喘恶化的影响,并阐明了其潜在机制。与 OVA 诱导的哮喘小鼠相比,暴露于 SiONPs 的小鼠的 Penh 值、炎性细胞计数和炎性细胞因子水平明显升高。暴露于 SiONPs 还导致气道炎症和黏液分泌增加,与 OVA 诱导的哮喘小鼠相比,硫氧还蛋白相互作用蛋白(TXNIP)、NOD 样受体 pyrin 结构域包含 3(NLRP3)炎性小体和白细胞介素(IL)-1β的蛋白表达水平增加。SiONPs 在 NCI-H292 细胞中的处理也显著增加了炎性细胞因子的 mRNA 表达水平,同时 TXNIP、NLRP3 炎性小体和 IL-1β 蛋白水平也呈浓度依赖性升高。总之,暴露于 SiONPs 会加重哮喘的发展,这与炎性小体的激活密切相关。我们的研究结果提供了有关 SiONPs 对哮喘恶化的毒理学影响的有用信息,并表明需要避免 SiONP 暴露,尤其是在患有呼吸系统疾病的人群中。