在工作场所条件下对个体进行短期超细金属烟雾颗粒受控暴露后，在其全血中以及体外人巨噬细胞中的人类长链非编码RNA CoroMarker、MALAT1、CDR1as和LINC00460 。
The human long noncoding RNAs CoroMarker, MALAT1, CDR1as, and LINC00460 in whole blood of individuals after controlled short-term exposure with ultrafine metal fume particles at workplace conditions, and in human macrophages in vitro.
作者信息
Scheurer Theresa, Steffens Jan, Markert Agnieszka, Du Marchie Sarvaas Miriam, Roderburg Christoph, Rink Lothar, Tacke Frank, Luedde Tom, Kraus Thomas, Baumann Ralf
机构信息
Institute for Occupational, Social and Environmental Medicine, Medical Faculty, University Hospital RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
Institute for Translational Medicine (ITM), Medical School Hamburg (MSH) - Am Kaiserkai 1, 20457, Hamburg, Germany.
出版信息
J Occup Med Toxicol. 2022 Aug 1;17(1):15. doi: 10.1186/s12995-022-00356-0.
BACKGROUND
Short-term inhalation of occupationally relevant ultrafine zinc/copper (Zn/Cu) containing welding fumes has been shown to induce subclinical systemic inflammation, associated with an elevated risk for cardiovascular diseases. The involvement of noncoding RNAs (lncRNAs) in this setting is currently unknown. However, lncRNAs have been reported to fulfill essential roles in, e.g., cardiovascular diseases, inflammation, infectious diseases, and pollution-related lung disorders.
METHODS
In this study, the specific lncRNAs levels of the 4 lncRNAs CoroMarker, MALAT1, CDR1as and LINC00460 were determined by RT-qPCR in THP-1 macrophages exposed to Zn/Cu metal fume suspensions for 1, 2, and 4 hours in vitro. Furthermore, 14 subjects were exposed to Zn/Cu containing welding fumes (at 2.5 mg/m) for 6 hours. Before, 6, 10, and 29 hours after exposure start, whole blood cell lncRNAs levels were determined by RT-qPCR.
RESULTS
In THP-1 macrophages, we observed a 2.3-fold increase of CDR1as at 1 h (Wilcoxon p = 0.03), a non-significant increase of CoroMarker at 1 h, and an increase of LINC00460 at 2 h (p = 0.03) and at 4 h (p = 0.06). In whole blood cells, we determined a non-significant upregulation of CDR1as at 6 h (p = 0.2), a significant downregulation of CoroMarker at 6 h (p = 0.04), and a significant upregulation of LINC00460 levels at 10 h (p = 0.04) and 29 h (p = 0.04). MALAT-1 remained unchanged in both settings.
CONCLUSION
The orientation of regulation of the lncRNAs is (except for CoroMarker) similar in the in vitro and in vivo experiments and in line with their described functions. Therefore, these results, e.g. the upregulation of the potential risk marker for cardiovascular diseases, CDR1as, contribute to understanding the underlying mechanisms of Zn/Cu-induced subclinical inflammation in metal workers.
背景
短期吸入与职业相关的含超细锌/铜（Zn/Cu）焊接烟尘已被证明会引发亚临床全身炎症，这与心血管疾病风险升高有关。目前尚不清楚非编码RNA（lncRNA）在这种情况下所起的作用。然而，据报道lncRNA在例如心血管疾病、炎症、传染病以及与污染相关的肺部疾病中发挥着重要作用。
方法
在本研究中，通过RT-qPCR测定了体外暴露于Zn/Cu金属烟尘悬浮液1小时、2小时和4小时的THP-1巨噬细胞中4种lncRNA（CoroMarker、MALAT1、CDR1as和LINC00460）的特定水平。此外，14名受试者暴露于含Zn/Cu的焊接烟尘（浓度为2.5mg/m³）6小时。在暴露开始前、暴露开始后6小时、10小时和29小时，通过RT-qPCR测定全血细胞lncRNA水平。
结果
在THP-1巨噬细胞中，我们观察到CDR1as在1小时时增加了2.3倍（Wilcoxon检验p = 0.03），CoroMarker在1小时时无显著增加，LINC00460在2小时时增加（p = 0.03）以及在4小时时增加（p = 0.06）。在全血细胞中，我们测定了CDR1as在6小时时无显著上调（p = 0.2），CoroMarker在6小时时显著下调（p = 0.04），以及LINC00460水平在10小时时显著上调（p = 0.04）和在29小时时显著上调（p = 0.04）。MALAT-1在两种情况下均保持不变。
结论
lncRNA的调控方向（除CoroMarker外）在体外和体内实验中相似，且与其所描述的功能一致。因此，这些结果，例如心血管疾病潜在风险标志物CDR1as的上调，有助于理解金属工人中Zn/Cu诱导的亚临床炎症的潜在机制。
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