Biomedical Sciences, Iowa State University, Ames, IA, 50011, USA.
Immunobiology Interdepartmental Graduate Program, Iowa State University, Ames, IA, 50011, USA.
Cell Tissue Res. 2021 Apr;384(1):129-148. doi: 10.1007/s00441-020-03333-3. Epub 2021 Jan 6.
Animal production units produce and store many contaminants on-site, including organic dust (OD) and hydrogen sulfide (HS). Workers in these settings report various respiratory disease symptoms. Both OD and HS have shown to induce lung inflammation. However, impact of co-exposure to both HS and OD has not been investigated. Therefore, we tested a hypothesis that pre-exposure to HS modulates the innate inflammatory response of the lungs to organic dust. In a mouse model of HS and organic dust extract (ODE) exposure, we assessed lung inflammation quantitatively. We exposed human airway epithelial and monocytic cells to medium or HS alone or HS followed by ODE and measured cell viability, oxidative stress, and other markers of inflammation. Exposure to 10 ppm HS followed by ODE increased the lavage fluid leukocytes. However, exposure to 10 ppm HS alone resulted in changes in tight junction proteins, an increase in mRNA levels of tlr2 and tlr4 as well as ncf1, ncf4, hif1α, and nrf2. HS alone or HS and ODE exposure decreased cell viability and increased reactive nitrogen species production. ODE exposure increased the transcripts of tlr2 and tlr4 in both in vitro and in vivo models, whereas increased nfkbp65 transcripts following exposure to ODE and HS was seen only in in vitro model. HS alone and HS followed by ODE exposure increased the levels of IL-1β. We conclude that pre-exposure to HS modulates lung innate inflammatory response to ODE.
动物生产单位会在现场产生和储存许多污染物，包括有机粉尘（OD）和硫化氢（HS）。在这些环境中工作的工人会报告出现各种呼吸道疾病症状。OD 和 HS 均已被证明可引发肺部炎症。然而，尚未研究过同时接触 HS 和 OD 的影响。因此，我们提出了一个假设，即 HS 预先暴露会调节肺部对有机粉尘的先天炎症反应。在 HS 和有机粉尘提取物（ODE）暴露的小鼠模型中，我们定量评估了肺部炎症。我们将人呼吸道上皮细胞和单核细胞暴露于培养基或 HS 中，或 HS 后暴露于 ODE 中，并测量细胞活力、氧化应激和其他炎症标志物。暴露于 10 ppm HS 后再暴露于 ODE 会增加灌洗液中的白细胞数。然而，单独暴露于 10 ppm HS 会导致紧密连接蛋白发生变化，tlr2 和 tlr4 的 mRNA 水平以及 ncf1、ncf4、hif1α 和 nrf2 增加。HS 单独或 HS 和 ODE 暴露会降低细胞活力并增加活性氮物种的产生。ODE 暴露会增加体外和体内模型中 tlr2 和 tlr4 的转录本，而仅在体外模型中观察到暴露于 ODE 和 HS 后 nfkbp65 转录本增加。HS 单独和 HS 后暴露于 ODE 会增加 IL-1β 的水平。我们得出结论，HS 预先暴露会调节肺部对 ODE 的先天炎症反应。
