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长非编码 RNA 介导短期 PM 暴露与全身炎症循环生物标志物之间的关联。

Long non-coding RNAs mediate the association between short-term PM exposure and circulating biomarkers of systemic inflammation.

机构信息

The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, China; Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 511436, China.

The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, China.

出版信息

Environ Pollut. 2023 Oct 15;335:122299. doi: 10.1016/j.envpol.2023.122299. Epub 2023 Aug 2.

DOI:10.1016/j.envpol.2023.122299
PMID:37541382
Abstract

Although short-term fine particulate matter (PM) exposure is associated with systemic inflammation, the effect of lncRNA on these association remains unknown. This study aims to investigate whether the plasma lncRNA mediate the effect of short-term PM exposure on systemic inflammation. In this cross-sectional study, plasma Clara cell protein 16 (CC16), interleukin 6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α) and lncRNA expression levels were measured in 161 adults between March and April in 2018 in Shijiazhuang, China. PM concentrations were estimated 0-3 days prior to the examination date and the moving averages were calculated. Multiple linear regressions were used to evaluate the associations between PM, the four biomarkers and lncRNA expression levels. Mediation analyses were performed to explore the potential roles of lncRNA expression in these associations. The median concentration of PM ranged from 39.65 to 60.91 mg/m across different lag days. The most significant effects on IL-6 and TNF-α per interquartile range increase in PM were observed at lag 0-3 days, with increases of 0.70 pg/mL (95% CI: 0.33, 1.07) and 0.21 pg/mL (95% CI: 0.06, 0.36), respectively. While the associations between PM and IL-8 (0.68 pg/mL, 95% CI: 0.34, 1.02) and CC16 (3.86 ng/mL, 95% CI: 1.60, 6.13) were stronger at lag 0 day. Interestingly, a negative association between PM and the expression of four novel lncRNAs (lnc-ACAD11-1:1, lnc-PRICKLE1-4:1, lnc-GPR39-7:2, and lnc-MTRNR2L12-3:6) were observed at each lag days. Furthermore, these lncRNAs mediated the effects of PM on the four biomarkers, with proportions of mediation ranged from 2.27% (95% CI: 1.19%, 9.82%) for CC16 to 35.60% (95% CI: 17.16%, 175.45%) for IL-6. Our findings suggested that plasma lncRNA expression mediat the acute effects of PM exposure on systematic inflammation. These highlight a need to consider circulating lncRNA expression as biomarkers to reduce health risks associated with PM.

摘要

尽管短期细颗粒物(PM)暴露与全身炎症有关,但长链非编码 RNA(lncRNA)对这些关联的影响尚不清楚。本研究旨在探讨血浆 lncRNA 是否介导短期 PM 暴露对全身炎症的影响。在这项横断面研究中,于 2018 年 3 月至 4 月在中国石家庄测量了 161 名成年人的血浆克拉拉细胞蛋白 16(CC16)、白细胞介素 6(IL-6)、白细胞介素 8(IL-8)、肿瘤坏死因子-α(TNF-α)和 lncRNA 表达水平。PM 浓度在检查日期前 0-3 天进行估计,并计算移动平均值。使用多元线性回归评估 PM 与四种生物标志物和 lncRNA 表达水平之间的关联。进行中介分析以探讨 lncRNA 表达在这些关联中的潜在作用。不同滞后天数的 PM 浓度中位数范围为 39.65-60.91 mg/m。PM 每增加一个四分位距,对 IL-6 和 TNF-α 的影响最大,分别为 0.70 pg/mL(95%CI:0.33,1.07)和 0.21 pg/mL(95%CI:0.06,0.36)。而 PM 与 IL-8(0.68 pg/mL,95%CI:0.34,1.02)和 CC16(3.86 ng/mL,95%CI:1.60,6.13)之间的关联在 0 天滞后时更强。有趣的是,在每个滞后日观察到 PM 与四种新的 lncRNA(lnc-ACAD11-1:1、lnc-PRICKLE1-4:1、lnc-GPR39-7:2 和 lnc-MTRNR2L12-3:6)的表达呈负相关。此外,这些 lncRNA 介导了 PM 对四种生物标志物的影响,CC16 的中介比例为 2.27%(95%CI:1.19%,9.82%),IL-6 为 35.60%(95%CI:17.16%,175.45%)。我们的研究结果表明,血浆 lncRNA 表达介导了 PM 暴露对系统性炎症的急性影响。这些结果表明,有必要将循环 lncRNA 表达作为生物标志物来降低与 PM 相关的健康风险。

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