Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Pediatrics, New Taipei Municipal TuCheng Hospital, New Taipei, Taiwan.
Ecotoxicol Environ Saf. 2024 Aug;281:116650. doi: 10.1016/j.ecoenv.2024.116650. Epub 2024 Jul 3.
Exposure to air pollutants has been associated with DNA damage and increases the risks of respiratory diseases, such as asthma and COPD; however short- and long-term effects of air pollutants on telomere dysfunction remain unclear. We investigated the impact of short- and long-term exposure to fine particulate matter with an aerodynamic diameter below 2.5 μm (PM) on telomere length in human bronchial epithelial BEAS-2B cells, and assessed the potential correlation between PM exposure and telomere length in the LIGHTS childhood cohort study. We observed that long-term, but not short-term, PM exposure was significantly associated with telomere shortening, along with the downregulation of human telomerase reverse transcriptase (hTERT) mRNA and protein levels. Moreover, long-term exposure to PM induced proinflammatory cytokine secretion, notably interleukin 6 (IL-6) and IL-8, triggered subG1 cell cycle arrest, and ultimately caused cell death. Long-term exposure to PM upregulated the LC3-II/ LC3-I ratio but led to p62 protein accumulation in BEAS-2B cells, suggesting a blockade of autophagic flux. Moreover, consistent with our in vitro findings, our epidemiological study found significant association between annual average exposure to higher PM and shortening of leukocyte telomere length in children. However, no significant association between 7-day short-term exposure to PM and leukocyte telomere length was observed in children. By combining in vitro experimental and epidemiological studies, our findings provide supportive evidence linking potential regulatory mechanisms to population level with respect to long-term PM exposure to telomere shortening in humans.
暴露于空气污染物与 DNA 损伤有关，并增加了呼吸道疾病（如哮喘和 COPD）的风险；然而，空气污染物对端粒功能障碍的短期和长期影响仍不清楚。我们研究了短期和长期暴露于空气动力学直径小于 2.5μm 的细颗粒物（PM）对人支气管上皮 BEAS-2B 细胞端粒长度的影响，并评估了 LIGHTS 儿童队列研究中 PM 暴露与端粒长度之间的潜在相关性。我们观察到，长期而非短期 PM 暴露与端粒缩短显著相关，同时下调人端粒酶逆转录酶（hTERT）mRNA 和蛋白水平。此外，长期暴露于 PM 会诱导促炎细胞因子的分泌，特别是白细胞介素 6（IL-6）和白细胞介素 8（IL-8），引发 subG1 细胞周期停滞，并最终导致细胞死亡。长期暴露于 PM 会增加 LC3-II/LC3-I 比值，但导致 BEAS-2B 细胞中 p62 蛋白积累，表明自噬流受阻。此外，与我们的体外研究结果一致，我们的流行病学研究发现，儿童年平均暴露于较高 PM 与白细胞端粒长度缩短之间存在显著关联。然而，在儿童中，7 天短期 PM 暴露与白细胞端粒长度之间没有显著关联。通过将体外实验和流行病学研究相结合，我们的研究结果提供了有说服力的证据，将潜在的调节机制与人群水平联系起来，说明长期 PM 暴露与人类端粒缩短有关。
