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Respirable stone particles differ in their ability to induce cytotoxicity and pro-inflammatory responses in cell models of the human airways
Particle and Fibre Toxicology ( IF 10 ) Pub Date : 2021-05-06 , DOI: 10.1186/s12989-021-00409-y
Vegard Sæter Grytting 1 , Magne Refsnes 1 , Johan Øvrevik 1 , Marit Sigrid Halle 2 , Jasmin Schönenberger 2 , Roelant van der Lelij 2 , Brynhild Snilsberg 3 , Tonje Skuland 1 , Richard Blom 4 , Marit Låg 1
Affiliation  

Respirable stone- and mineral particles may be a major constituent in occupational and ambient air pollution and represent a possible health hazard. However, with exception of quartz and asbestos, little is known about the toxic properties of mineral particles. In the present study, the pro-inflammatory and cytotoxic responses to six stone particle samples of different composition and with diameter below 10 μm were assessed in human bronchial epithelial cells (HBEC3-KT), THP-1 macrophages and a HBEC3-KT/THP-1 co-culture. Moreover, particle-induced lysis of human erythrocytes was assessed to determine the ability of the particles to lyse biological membranes. Finally, the role of the NLRP3 inflammasome was assessed using a NLRP3-specific inhibitor and detection of ASC oligomers and cleaved caspase-1 and IL-1β. A reference sample of pure α-quartz was included for comparison. Several stone particle samples induced a concentration-dependent increase in cytotoxicity and secretion of the pro-inflammatory cytokines CXCL8, IL-1α, IL-1β and TNFα. In HBEC3-KT, quartzite and anorthosite were the most cytotoxic stone particle samples and induced the highest levels of cytokines. Quartzite and anorthosite were also the most cytotoxic samples in THP-1 macrophages, while anorthosite and hornfels induced the highest cytokine responses. In comparison, few significant differences between particle samples were detected in the co-culture. Adjusting responses for differences in surface area concentrations did not fully account for the differences between particle samples. Moreover, the stone particles had low hemolytic potential, indicating that the effects were not driven by membrane lysis. Pre-incubation with a NLRP3-specific inhibitor reduced stone particle-induced cytokine responses in THP-1 macrophages, but not in HBEC3-KT cells, suggesting that the effects are mediated through different mechanisms in epithelial cells and macrophages. Particle exposure also induced an increase in ASC oligomers and cleaved caspase-1 and IL-1β in THP-1 macrophages, confirming the involvement of the NLRP3 inflammasome. The present study indicates that stone particles induce cytotoxicity and pro-inflammatory responses in human bronchial epithelial cells and macrophages, acting through NLRP3-independent and -dependent mechanisms, respectively. Moreover, some particle samples induced cytotoxicity and cytokine release to a similar or greater extent than α-quartz. Thus, these minerals warrant further attention in future research.

中文翻译:

可吸入石颗粒在人类呼吸道细胞模型中诱导细胞毒性和促炎反应的能力不同

可吸入的石头和矿物颗粒可能是职业和环境空气污染的主要成分,并可能对健康造成危害。然而,除了石英和石棉,人们对矿物颗粒的毒性知之甚少。在本研究中,在人支气管上皮细胞 (HBEC3-KT)、THP-1 巨噬细胞和 HBEC3-KT/THP 中评估了对六种不同成分且直径小于 10 μm 的结石颗粒样品的促炎和细胞毒性反应。 -1 共文化。此外,评估了颗粒诱导的人红细胞裂解以确定颗粒裂解生物膜的能力。最后,使用 NLRP3 特异性抑制剂和检测 ASC 寡聚体和裂解的 caspase-1 和 IL-1β 来评估 NLRP3 炎症小体的作用。包括纯α-石英参考样品进行比较。几个结石颗粒样品诱导促炎细胞因子 CXCL8、IL-1α、IL-1β 和 TNFα 的细胞毒性和分泌的浓度依赖性增加。在 HBEC3-KT 中,石英岩和斜长岩是最具细胞毒性的石头颗粒样品,并诱导最高水平的细胞因子。石英岩和斜长岩也是 THP-1 巨噬细胞中细胞毒性最强的样品,而斜长岩和角岩诱导最高的细胞因子反应。相比之下,在共培养物中检测到颗粒样品之间几乎没有显着差异。调整表面积浓度差异的响应并没有完全说明颗粒样品之间的差异。此外,石颗粒具有低溶血潜力,表明效果不是由膜裂解驱动的。与 NLRP3 特异性抑制剂预孵育降低了 THP-1 巨噬细胞中石颗粒诱导的细胞因子反应,但在 HBEC3-KT 细胞中没有降低,这表明这些作用是通过上皮细胞和巨噬细胞中的不同机制介导的。颗粒暴露还诱导 THP-1 巨噬细胞中 ASC 寡聚体和裂解的 caspase-1 和 IL-1β 增加,证实了 NLRP3 炎症小体的参与。本研究表明,石颗粒分别通过 NLRP3 独立和依赖机制在人支气管上皮细胞和巨噬细胞中诱导细胞毒性和促炎反应。此外,一些颗粒样品诱导细胞毒性和细胞因子释放的程度与 α-石英相似或更大。因此,
更新日期:2021-05-06
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