Bioanalytical and Pharmacokinetic Research Group, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.
Department of Human and Environmental Toxicology, University of Science and Technology, Daejeon 34113, Republic of Korea.
Int J Environ Res Public Health. 2023 Mar 8;20(6):4766. doi: 10.3390/ijerph20064766.
Because of their exposure to air, eyes can come into contact with air pollutants such as particulate matter (PM), which may cause severe ocular pathologies. Prolonged ocular PM exposure may increase inflammation and endoplasmic reticulum stress in the retina. Herein, we investigated whether PM exposure induces ocular inflammation and endoplasmic reticulum (ER) stress-related cellular responses in human retinal epithelium-19 (ARPE-19) cells. To understand how PM promotes ocular inflammation, we monitored the activation of the mitogen-activated protein kinase (MAPK)/nuclear factor kappa beta (NFκB) axis and the expression of key inflammatory mRNAs. We also measured the upregulation of signature components for the ER-related unfolded protein response (UPR) pathways, as well as intracellular calcium ([Ca]) levels, as readouts for ER stress induction following PM exposure. Ocular PM exposure significantly elevated the expression of multiple cytokine mRNAs and increased phosphorylation levels of NFκB-MAPK axis in a PM dose-dependent manner. Moreover, incubation with PM significantly increased [Ca] levels and the expression of UPR-related proteins, which indicated ER stress resulting from cell hypoxia, and upregulation of hypoxic adaptation mechanisms such as the ER-associated UPR pathways. Our study demonstrated that ocular PM exposure increased inflammation in ARPE-19 cells, by activating the MAPK/NFκB axis and cytokine mRNA expression, while also inducing ER stress and stress adaptation responses. These findings may provide helpful insight into clinical and non-clinical research examining the role of PM exposure in ocular pathophysiology and delineating its underlying molecular mechanisms.
由于眼睛暴露在空气中，它们可能会接触到空气中的污染物，如颗粒物 (PM)，这可能会导致严重的眼部疾病。长时间暴露于眼内 PM 可能会增加视网膜中的炎症和内质网应激。在此，我们研究了 PM 暴露是否会引起人视网膜色素上皮细胞-19（ARPE-19）细胞的眼部炎症和内质网 (ER) 应激相关的细胞反应。为了了解 PM 如何促进眼部炎症，我们监测了丝裂原活化蛋白激酶 (MAPK)/核因子 kappa B (NFκB) 轴的激活和关键炎症 mRNA 的表达。我们还测量了 ER 相关未折叠蛋白反应 (UPR) 途径的标志性成分的上调，以及细胞内钙 ([Ca]) 水平，作为 PM 暴露后 ER 应激诱导的读数。眼部 PM 暴露显著上调了多种细胞因子 mRNA 的表达，并呈 PM 剂量依赖性增加 NFκB-MAPK 轴的磷酸化水平。此外，PM 孵育显著增加了 [Ca]水平和 UPR 相关蛋白的表达，这表明细胞缺氧导致 ER 应激，以及缺氧适应机制（如 ER 相关 UPR 途径）的上调。我们的研究表明，眼部 PM 暴露通过激活 MAPK/NFκB 轴和细胞因子 mRNA 表达，增加了 ARPE-19 细胞的炎症，同时还诱导了 ER 应激和应激适应反应。这些发现可能为研究 PM 暴露在眼部病理生理学中的作用及其潜在分子机制的临床和非临床研究提供有价值的见解。
