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颗粒物暴露通过增加呼吸道合胞病毒感染的人肺类器官中的应激颗粒形成来加剧细胞损伤。

Particulate matter exposure exacerbates cellular damage by increasing stress granule formation in respiratory syncytial virus-infected human lung organoids.

机构信息

Department of Biochemistry, Chungnam National University, Daejeon, 34134, Republic of Korea.

Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, 34114, Republic of Korea.

出版信息

Environ Pollut. 2022 Dec 15;315:120439. doi: 10.1016/j.envpol.2022.120439. Epub 2022 Oct 15.

DOI:10.1016/j.envpol.2022.120439
PMID:36257563
Abstract

Exposure to atmospheric particulate matter (PM) increases morbidity and mortality in respiratory diseases by causing various adverse health effects; however, the effects of PM exposure on cellular stress under virus-infected conditions remain unclear. The effects of PM under 10 μm (PM) and diesel PM (DPM) on respiratory syncytial virus (RSV) infection were investigated in human two-dimensional lung epithelial cells and human three-dimensional lung organoids mimicking the lung tissue. We evaluated the formation of stress granules, which are important in cellular adaptation to various stress conditions. Furthermore, we investigated the effects of repeated exposure to PM and DPM on DNA damage and cell death during viral infection. PM and DPM did not cause stress granule formation in the absence of RSV infection but drastically increased stress granule formation and signal transduction during RSV infection in human lung epithelial cells and human lung organoids. Further, repeated exposure to PM and DPM caused cell death by severely damaging DNA under RSV infection conditions. Thus, PM and DPM induce severe lung toxicity under stress conditions, such as viral infection, suggesting that the effects of PMs under various stressful conditions should be examined to accurately predict the lung toxicity of PM.

摘要

大气颗粒物(PM)暴露通过引起各种不良健康影响,增加呼吸道疾病的发病率和死亡率;然而,PM 暴露对病毒感染条件下细胞应激的影响仍不清楚。在模拟肺部组织的二维人肺上皮细胞和三维肺类器官中,研究了 10 μm 以下颗粒物(PM)和柴油机颗粒物(DPM)对呼吸道合胞病毒(RSV)感染的影响。我们评估了应激颗粒的形成,这在细胞适应各种应激条件中很重要。此外,我们研究了在病毒感染期间,PM 和 DPM 重复暴露对 DNA 损伤和细胞死亡的影响。在没有 RSV 感染的情况下,PM 和 DPM 不会引起应激颗粒的形成,但在 RSV 感染的人肺上皮细胞和肺类器官中,PM 和 DPM 会显著增加应激颗粒的形成和信号转导。此外,在 RSV 感染条件下,PM 和 DPM 的重复暴露会严重破坏 DNA 导致细胞死亡。因此,PM 和 DPM 在应激条件下(如病毒感染)会引起严重的肺部毒性,这表明应在各种应激条件下检查 PM 的影响,以准确预测 PM 的肺部毒性。

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