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首页> 外文期刊>Cell and Tissue Research >Organic dust-induced mitochondrial dysfunction could be targeted via cGAS-STING or cytoplasmic NOX-2 inhibition using microglial cells and brain slice culture models
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Organic dust-induced mitochondrial dysfunction could be targeted via cGAS-STING or cytoplasmic NOX-2 inhibition using microglial cells and brain slice culture models

机译：有机粉尘诱导的线粒体功能障碍可以通过CGA-Sting或细胞质NOx-2抑制来靶向，使用微胶质细胞和脑切片培养模型

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Organic dust (OD) exposure in animal production industries poses serious respiratory and other health risks. OD consisting of microbial products and particulate matter and OD exposure-induced respiratory inflammation are under investigation. However, the effect of OD exposure on brain remains elusive. We show that OD exposure of microglial cells induces an inflammatory phenotype with the release of mitochondrial DNA (mt-DNA). Therefore, we tested a hypothesis that OD exposure-induced secreted mt-DNA signaling drives the inflammation. A mouse microglial cell line was treated with medium or organic dust extract (ODE, 1% v/v) along with either phosphate-buffered saline (PBS) or mitoapocynin (MA, 10 mu mol). Microglia treated with control or anti-STING siRNA were exposed to medium or ODE. Mouse organotypic brain slice cultures (BSCs) were exposed to medium or ODE with or without MA. Various samples were processed to quantify mitochondrial reactive oxygen species (mt-ROS), mt-DNA, cytochrome c, TFAM, mitochondrial stress markers and mt-DNA-induced signaling via cGAS-STING and TLR9. Data were analyzed and a p value of <= 0.05 was considered significant. MA treatment decreased the ODE-induced mt-DNA release into the cytosol. ODE increased MFN1/2 and PINK1 but not DRP1 and MA treatment decreased the MFN2 expression. MA treatment decreased the ODE exposure-induced mt-DNA signaling via cGAS-STING and TLR9. Anti-STING siRNA decreased the ODE-induced increase in IRF3, IFN-beta and IBA-1 expression. In BSCs, MA treatment decreased the ODE-induced TNF-alpha, IL-6 and MFN1. Therefore, OD exposure-induced mt-DNA signaling was curtailed through cytoplasmic NOX-2 inhibition or STING suppression to reduce brain microglial inflammatory response.
机译：动物生产行业中的有机粉尘（OD）暴露会造成严重的呼吸和其他健康风险。目前正在调查由微生物产物和颗粒物组成的OD以及OD暴露引起的呼吸道炎症。然而，OD暴露对大脑的影响仍不清楚。我们发现，OD暴露于小胶质细胞可通过释放线粒体DNA（mt DNA）诱导炎症表型。因此，我们检验了OD暴露诱导分泌的mt DNA信号驱动炎症的假说。用培养基或有机粉尘提取物（ODE，1%v/v）以及磷酸盐缓冲盐水（PBS）或丝裂霉素（MA，10μmol）处理小鼠小胶质细胞系。用对照或抗STING siRNA处理的小胶质细胞暴露于培养基或ODE中。小鼠器官型脑切片培养（BSC）暴露于含或不含MA的培养基或ODE中。对各种样本进行处理，以量化线粒体活性氧物种（mt ROS）、mt DNA、细胞色素c、TFAM、线粒体应激标记物以及通过cGAS STING和TLR9的mt DNA诱导信号。对数据进行分析，认为p值<=0.05是显著的。MA处理降低了ODE诱导的mt DNA释放到胞浆中。ODE增加MFN1/2和PINK1，但不增加DRP1，MA处理降低MFN2的表达。MA处理通过cGAS STING和TLR9降低ODE暴露诱导的mt-DNA信号。抗STING siRNA降低了ODE诱导的IRF3、IFN-β和IBA-1表达的增加。在BSC中，MA治疗降低了ODE诱导的TNF-α、IL-6和MFN1。因此，OD暴露诱导的mt DNA信号通过抑制细胞质NOX-2或STING来减少脑小胶质细胞炎症反应。

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