Department of Anatomy, Quanzhou Medical College.
Department of Environmental Medicine, Quanzhou Medical College.
Biomed Res. 2022;43(1):23-30. doi: 10.2220/biomedres.43.23.
Air pollution is associated with increased morbidity and mortality and with cell death at a cellular level. However, the exact mechanism of particulate matter-induced cell death remains to be elucidated. The aim of the present in vitro study using human alveolar epithelial cells (A549) was to determine the cell death pathway(s) induced by black carbon (BC) and ozone oxidized-black carbon (O-BC). BC and O-BC induced A549 cell death and the cytotoxic effect was dose-dependent. Cell death was significantly abrogated by inhibitor of receptor protein interacting kinase 1 (RIPK1) but only mildly inhibited by apoptosis inhibitor and RIPK3. BC- and O-BC-treated cells showed RIPK1 and RIPK3 protein overexpression and high phosphorylated levels of these proteins, as well as detectable levels of caspase-8 active form. BC- and O-BC-triggered cell death was also fully rescued in A549 cells that under-expressed RIPK1 with RIPK1 siRNA. Our results indicated that BC and O-BC could induce cell death through a multitude of pathways including apoptotic and necroptotic pathways and that RIPK1 is the upstream signal protein of these cell death pathways, with an important role in the regulation of BC-induced cell death.
空气污染与发病率和死亡率的增加以及细胞水平的细胞死亡有关。然而，颗粒物质诱导细胞死亡的确切机制仍有待阐明。本体外研究使用人肺泡上皮细胞（A549）的目的是确定黑碳（BC）和臭氧氧化黑碳（O-BC）诱导的细胞死亡途径。BC 和 O-BC 诱导 A549 细胞死亡，细胞毒性作用呈剂量依赖性。受体蛋白相互作用激酶 1（RIPK1）抑制剂显著阻断细胞死亡，但凋亡抑制剂和 RIPK3 仅轻度抑制。BC 和 O-BC 处理的细胞显示 RIPK1 和 RIPK3 蛋白过表达以及这些蛋白的高磷酸化水平，以及可检测到的 caspase-8 活性形式。用 RIPK1 siRNA 下调 RIPK1 的 A549 细胞可完全挽救 BC 和 O-BC 触发的细胞死亡。我们的结果表明，BC 和 O-BC 可通过多种途径诱导细胞死亡，包括凋亡和坏死途径，并且 RIPK1 是这些细胞死亡途径的上游信号蛋白，在调节 BC 诱导的细胞死亡中起重要作用。
