Abstract：
In recent years, carbonized silicon nanoparticles (SiC NPs) have found widespread scientific and engineering applications, raising concerns about potential human health risks. SiC NPs may induce pulmonary damage through sustained inflammatory responses and oxidative stress, with unclear toxicity mechanisms. This study uses an in vitro co-culture model of alveolar macrophages (NR8383) and alveolar epithelial cells (RLE-6TN) to simulate the interaction between airway epithelial cells and immune cells, providing initial insights into SiC NP-triggered inflammatory responses. The research reveals that increasing SiC NP exposure prompts NR8383 cells to release high mobility group box 1 protein (HMGB1), which migrates into RLE-6TN cells and activates the receptor for advanced glycation end-products (RAGE) and Toll-like receptor 4 (TLR4). RAGE and TLR4 synergistically activate the MyD88/NF-κB inflammatory pathway, ultimately inducing inflammatory responses and oxidative stress in RLE-6TN cells, characterized by excessive ROS generation and altered cytokine levels. Pretreatment with RAGE and TLR4 inhibitors attenuates SiC-induced HMGB1 expression and downstream pathway proteins, reducing inflammatory responses and oxidative damage. This highlights the pivotal role of RAGE-TLR4 crosstalk in SiC NP-induced pulmonary inflammation, providing insights into SiC NP cytotoxicity and nanomaterial safety guidelines.
摘要：
近年来,碳化硅纳米颗粒(SiCNPs)已经发现了广泛的科学和工程应用，引起人们对潜在人类健康风险的担忧。SiCNPs可能通过持续的炎症反应和氧化应激诱导肺损伤,毒性机制不清楚。本研究采用肺泡巨噬细胞(NR8383)和肺泡上皮细胞(RLE-6TN)的体外共培养模型,模拟气道上皮细胞与免疫细胞的相互作用,提供对SiCNP触发的炎症反应的初步见解。研究表明，增加SiCNP暴露促使NR8383细胞释放高迁移率族蛋白1（HMGB1），它迁移到RLE-6TN细胞并激活晚期糖基化终产物（RAGE）和Toll样受体4（TLR4）的受体。RAGE和TLR4协同激活MyD88/NF-κB炎症通路，最终诱导RLE-6TN细胞的炎症反应和氧化应激，以过量的ROS产生和改变的细胞因子水平为特征。用RAGE和TLR4抑制剂预处理减弱SiC诱导的HMGB1表达和下游途径蛋白，减少炎症反应和氧化损伤。这突出了RAGE-TLR4串扰在SiCNP诱导的肺部炎症中的关键作用，提供对SiCNP细胞毒性和纳米材料安全指南的见解。
