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镉暴露工人免疫标志物变化与 microRNA 表达的关联。

Association of microRNA expression with changes in immune markers in workers with cadmium exposure.

机构信息

Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India.

Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India.

出版信息

Chemosphere. 2021 Jul;274:129615. doi: 10.1016/j.chemosphere.2021.129615. Epub 2021 Jan 26.

Abstract

Human exposure to cadmium (Cd) is known to produce severe health effects. Recently, molecular mechanism of Cd toxicity has revealed the role of Cd in causing epigenetic alterations. miRNAs are small, non-coding RNAs which are involved in translational repression of genes. Therefore, the aim of the present study was to evaluate the alterations in expression of miRNAs associated with inflammation, carcinogenesis and, further, study their possible correlation with immune profile, in occupationally Cd exposed workers of Jodhpur. 106 workers from metal handicraft and welding factories were recruited as subjects, while, 80 apparently healthy non-exposed individuals served as control for this study. Blood Cd levels (BCd) were determined by Graphite Furnace Atomic Absorption Spectroscopy (GFAAS). Lymphocyte cell subset were measured by flow cytometry, serum interleukins were assessed by ELISA and miRNA expression was determined by Real Time Polymerase Chain Reaction (RT-PCR). BCd levels were significantly higher in the exposed individuals when compared to the non-exposed, with welders reporting the highest amongst all. Among the lymphocyte subset, exposed group showed significantly higher percentage of Th17 and lower percentage of Treg population. Cytokine profile expressed by exposed workers were predominantly pro-inflammatory in nature. Among, the studied miRNAs, miR-221 was significantly higher in exposed group with a fold change of 3.05. Additionally, miR-221 and miR-155 showed significant positive correlation with Th17 cell %. Regression analysis showed duration of exposure and IL-17 to have significant effect on miR-221 in exposed group. In conclusion, miR-221 was significantly upregulated in exposed and was correlated with immune alteration making it a potential candidate for further exploration of mechanism underlying Cd toxicity.

摘要

人体接触镉(Cd)已知会产生严重的健康影响。最近,Cd 毒性的分子机制揭示了 Cd 导致表观遗传改变的作用。miRNA 是小的非编码 RNA,参与基因的翻译抑制。因此,本研究旨在评估与炎症、致癌作用相关的 miRNA 的表达变化,并进一步研究它们与职业性 Cd 暴露工人的免疫特征的可能相关性。在焦特布尔,从金属手工艺品和焊接工厂招募了 106 名工人作为研究对象,而 80 名明显健康的非暴露个体作为对照组。采用石墨炉原子吸收光谱法(GFAAS)测定血液 Cd 水平(BCd)。采用流式细胞术测定淋巴细胞亚群,采用 ELISA 测定血清白细胞介素,采用实时聚合酶链反应(RT-PCR)测定 miRNA 表达。与非暴露者相比,暴露者的 BCd 水平显著升高,其中焊工的水平最高。在淋巴细胞亚群中,暴露组的 Th17 比例显著升高,Treg 比例显著降低。暴露组的细胞因子谱以促炎为主。在所研究的 miRNA 中,miR-221 在暴露组中的表达显著升高,倍数变化为 3.05。此外,miR-221 和 miR-155 与 Th17 细胞百分比呈显著正相关。回归分析显示,暴露组的暴露时间和 IL-17 对 miR-221 有显著影响。总之,miR-221 在暴露组中显著上调,并与免疫改变相关,使其成为进一步探索 Cd 毒性机制的潜在候选者。

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