石英粉尘激活TLR4信号通路诱导气道炎症反应的机制研究
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P579

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国家自然科学基金项目(41472046;41602033);四川省科技计划项目(2016JY0045)


Mechanism of TLR4 signaling pathway activated by quartz dust to induce airway inflammation
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    摘要:

    为了探索大气颗粒物中石英粉尘诱导气道炎症反应的分子机制,采用XRD对石英粉尘进行了物相分析,并以支气管上皮细胞作为染毒对象,将石英粉尘作用于细胞24 h后,CCK-8检测细胞存活率,ELISA检测培养上清液中的白细胞介素-6(IL-6)和白细胞介素-8(IL-8)的浓度,Western Blot检测TLR4的表达,使用Toll样受体4特异性抑制剂TAK 242预处理后检测IL-6、IL-8、TLR4水平。实验结果显示,石英粉尘的主要物相是石英,并含部分方解石;随着石英粉尘染毒浓度的增加,细胞相对存活率下降;与对照组相比,100 μg/mL组上清液中IL-6与IL-8浓度显著增加(P<0.01);50、75和100 μg/mL组的高水平IL-6和IL-8可被TAK 242拮抗,使用TAK 242预处理后,100 μg/mL组IL-6、IL-8浓度显著降低(P<0.01);TLR4的表达量随石英粉尘浓度增加而升高,且TAK 242的干预可以有效阻止TLR4通路的活化。研究结果表明,石英粉尘可以刺激支气管上皮细胞分泌高浓度的炎症因子,其机制可能是TLR4信号通路的活化。

    Abstract:

    To explore the molecular mechanism of quartz dust in the atmospheric particulates exacerbating respiratory inflammatory response, the authors used XRD to analyze the phase of quartz dust, and utilized bronchial epithelial cells as the target. After the cells were treated by quartz dust for 24 h, CCK-8 was used to detect cell viability and the concentration of interleukin-6 (IL-6) and interleukin-8 in the culture supernatant was detected by ELISA. Western Blot was used to detect the expression of TLR4. The levels of IL-6, IL-8 and TLR4 were detected after being pretreated with Toll like receptor 4 specific inhibitor TAK 242. According to the results, the main phase of quartz dust was quartz, including partial calcite; the relative cell survival ratio decreased with the increase of quartz dust concentration; the concentration of IL-6 and IL-8 in the supernatant of the 100 μg/mL group was significantly increased compared with the control group (P<0.01); high levels of IL-6 and IL-8 in the 50, 75, and 100 μg/mL groups were antagonized by TAK 242; after being pretreated with TAK 242, IL-6 and IL-8 were significantly reduced in the 100 μg/mL group (P<0.01); the expression of TLR4 increased with the increase of quartz dust concentration, and the intervention of TAK 242 could effectively prevent the activation of TLR4 pathway. In summary, it can be concluded that exposure to quartz dust can stimulate the secretion of high concentrations of inflammatory factors in bronchial epithelial cells, and the mechanism may be the activation of TLR4 signaling pathway.

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陈祥娃,霍婷婷,董发勤,刘靳波,邓建军,2020,石英粉尘激活TLR4信号通路诱导气道炎症反应的机制研究[J].岩石矿物学杂志,39(2):211~217.

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  • 收稿日期:2019-08-27
  • 最后修改日期:2019-11-13
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  • 在线发布日期: 2020-03-10
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