Yen Pei-Ling, Yang Cai-Ru, Huang Mei-Lun, Lin Ting-An, Liao Vivian Hsiu-Chuan
Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 106, Taiwan.
Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 106, Taiwan.
Environ Toxicol Pharmacol. 2023 Mar;98:104071. doi: 10.1016/j.etap.2023.104071. Epub 2023 Jan 20.
Di(2-ethylhexyl) phthalate (DEHP), a widespread contaminant, has numerous adverse impacts on human health and ecosystems. Chronic DEHP exposure has been found to accelerate aging; however, its potential threat to age-dependent innate immune decline remains unknown. This study aims to evaluate the effects of chronic DEHP exposure on innate immunosenescence in Caenorhabditis elegans. We show that the length of the exposure period significantly impacts DEHP-induced age-related declines, which is linked to immunosenescence and oxidative stress. We found that the DEHP-caused immunosenescence is accompanied with downregulation of an antimicrobial gene lys-7 as well as an enhancement of the nuclear translocation of HLH-30, an orthologue of mammalian transcription factor EB (TFEB). Moreover, DEHP exposure increases the expression of riok-1, a human RIO kinase homolog, which is associated with DEHP-induced HLH-30/TFEB translocation. Our findings suggest that early-life and chronic exposure to DEHP, mostly due to parent compound rather than its metabolite mono(2-ethylhexyl) phthalate (MEHP), may weaken the innate immunity in C. elegans and may enhance susceptibility to infections or promote immunosenescence in aged populations.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种广泛存在的污染物，对人类健康和生态系统有诸多不利影响。已发现长期接触DEHP会加速衰老；然而，其对年龄依赖性先天免疫衰退的潜在威胁仍不明确。本研究旨在评估长期接触DEHP对秀丽隐杆线虫先天免疫衰老的影响。我们发现，接触期的长短会显著影响DEHP诱导的与年龄相关的衰退，这与免疫衰老和氧化应激有关。我们发现，DEHP导致的免疫衰老伴随着抗菌基因lys-7的下调以及HLH-30核转位的增强，HLH-30是哺乳动物转录因子EB（TFEB）的同源物。此外，接触DEHP会增加人类RIO激酶同源物riok-1的表达，这与DEHP诱导的HLH-30/TFEB转位有关。我们的研究结果表明，生命早期长期接触DEHP，主要是由于母体化合物而非其代谢产物单（2-乙基己基）邻苯二甲酸酯（MEHP），可能会削弱秀丽隐杆线虫的先天免疫力，并可能增加老年人群对感染的易感性或促进免疫衰老。
